Non-Thermal Ablation System for Treating Tissue

ABSTRACT

Systems and methods for non-thermal ablation of tissue are provided. A non-implantable minimally invasive system for treatment of tissue in a body via direct current ablation is provided including a catheter, a plurality of electrodes for deployment through the catheter, a power source for applying power to the electrodes, and a fixation element for maintaining the catheter in a treatment position during treatment of the tissue. A minimally invasive method for treating tissue in a body via direct current ablation is provided including inserting a catheter into the body such that a portion of the catheter remains outside of the body, deploying a fixation element to fix the catheter in a treatment position, deploying a plurality of electrodes through the catheter, applying power to the plurality of electrodes, using the electrodes to apply a current to the tissue, and removing the catheter from the body.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent ApplicationNos. 61/090,589, filed Aug. 20, 2008; 61/090,519, filed Aug. 20, 2008;61/090,594, filed Aug. 20, 2008; and 61/090,600, filed Aug. 20, 2008;and is related to the following U.S. patent applications:

Ser. No. ______ entitled “Non-Thermal Ablation System for Treating BPHand Other Growths”, filed on Aug. 18, 2009 (Attorney Docket No.190417/US/2);

Ser. No. ______, entitled “Low-Corrosion Electrode for Treating Tissue”,filed on Aug. 18, 2009 (Attorney Docket No. 190418/US/2);

Ser. No. ______, entitled “Catheter for Treating Tissue with Non-ThermalAblation”, filed on Aug. 18, 2009 (Attorney Docket No. 190419/US/2).

The contents of each of the above listed applications are herebyincorporated by reference herein in their entireties.

FIELD OF THE INVENTION

The present invention relates generally to systems and methods fortreating tissue and, more specifically, to non-thermal ablation systemsand methods for treating tissue.

BACKGROUND

Enlargement of the prostate gland (known as benign prostatic hyperplasiaor hypertrophy—“BPH”) is a common ailment in older men. BPH affects 40%of men in their 50s and 90% of men in their 80s. The enlargement of theprostate is a form of benign tumor or adenoma. FIG. 1 illustrates asimplified view of the anatomy and location of the prostate 3, 4. Theurethra 1 passes upwards through the external urethral sphincter 2,through the prostate 3, 4 (surrounding the urethra), and into thebladder 5. The prostate 3, 4 comprises three lobes: two major lobes 3, 4and a median lobe. The median lobe is located generally behind the majorlobes 3, 4.

As the prostate becomes enlarged, it may compress the urethra and causeone or more of the following symptoms to occur: more frequent urination,weak urine stream, inability to delay urination, difficulty starting andstopping urination, incomplete emptying of the bladder, loss of bladdercontrol, and painful or bloody urination.

If symptoms are mild and do not affect quality of life, treatment maynot be performed. If diagnosed with BPH but not pursuing treatmentoptions, men typically receive regular checkups and report increased BPHsymptoms to the physician. If symptoms occur and cause discomfort,affect activities of daily living, or endanger health, drug treatment orsurgery may be recommended. Treatment options for BPH include lifestylechanges (such as adjusting fluid intake), herbal remedies, drug therapy,non-surgical procedures, and surgical procedures. The goals of treatmentare generally to improve urinary flow and decrease symptoms associatedwith BPH. Treatment may delay or prevent the progression of BPH.

Drugs may be used to relieve the common urinary symptoms associated withBPH by either reducing the size of the prostate gland or by slowing thegrowth of the prostate. Common drug classes used to treat urinarysymptoms include alpha blockers, such as doxazosin or tamsulosin, and5-alpha reductase inhibitors, such as finasteride or dutasteride. Themedications may have deleterious side effects such as decreased libido,impotence, retrograde ejaculation, fatigue, dizziness, headache, anddecreased blood pressure. If drug therapy does not provide adequaterelief of symptoms, surgery may be needed to help correct the prostategland overgrowth. Further, if more severe symptoms of BPH present, suchas recurrent urinary retention, recurrent blood in the urine, recurrenturinary tract infections or bladder stones, drug therapy should not beinitiated. Generally, upon presentation of these symptoms, surgery isindicated.

Surgical treatments of BPH may or may not be minimally invasive. For thesurgical methods, access to the prostate may be via the urethra, theperineum, or other route.

Non-minimally invasive surgical treatments include Trans UrethralResection of the Prostate (TURP). Conducted in an operating room undergeneral or spinal anesthetic, a probe is passed through the urethrawhich scrapes away prostate tissue causing the blockage. Side effectsmay include retrograde ejaculation, impotence, and a repeat of theprocedure if the blockage regrows. U.S. Pat. No. 6,491,672, hereinincorporated by reference, discloses one surgery option for treatingBPH.

Minimally invasive surgical treatments usually offer the incentives ofless pain, faster recovery, lower costs, and use of local anesthesia anda mild sedative. In general, minimally invasive surgical treatmentsdestroy prostate tissue through one of various mechanisms. The destroyedprostate tissue may be reabsorbed by the body and/or discharged into theurine over a period of time. Minimally-invasive surgical treatmentoptions include generation of heat, freezing, chemical means, andultrasound to destroy prostate tissue. Care must be taken to avoiddamaging sensitive areas adjacent the prostate such as nervescontrolling sexual functions or the rectal wall.

Various types of laser treatment of BPH exist including laserprostatectomy, interstitial laser coagulation, photosensitivevaporization of the prostate, Holmium laser ablation of the prostate,and Holmium laser enucleation of the prostate (HoLEP). Laserprostatectomy uses a transurethral laser device to cut or vaporizeobstructions. Interstitial Laser Coagulation uses a cystoscope throughwhich a fiberoptic probe is directly introduced into the prostate. Asmall laser fiber is inserted into the prostate through the deviceinserted in the urethra. Laser energy heats a selected area and theprobe may be moved several times to treat all areas of obstruction.Photosensitive vaporization of the prostate (PVP) uses a laser deliveredthrough an endoscope inserted into the urethra. The high-energy laservaporizes excess prostate tissue and seals the treated area.

For microwave treatment of BPH, a microwave antenna is insertedtransurethrally into the prostate. Various forms of microwave treatmentmay include a cooling means for minimizing patient discomfort and toprotect adjacent urethral tissue from damage. Further means may be usedto dilate the urethra.

Heat for treatment of BPH may be generated, for example, via laserbeams, microwaves, radiofrequency current, or direct current. Other heatapplication techniques exist for treating BPH including transurethralvaporization of the prostate (TUVP) wherein heat is applied directly tothe prostate with a grooved roller bar that vaporizes tissue andwater-induced thermotherapy (WIT) to destroy obstructive tissue whereinhot water flows through a transurethrally-placed balloon. U.S. Pat. Nos.5,928,225 and 6,640,139, herein incorporated by reference in theirentirety, further disclose treatment methods using heat.

Non-thermal treatments of BPH include injection of ethanol (see, forexample, U.S. Pat. No. 7,015,253) or direct current ablation (see, forexample, U.S. Pat. Nos. 7,079,890; 6,733,485; and 6,901,294).

Transurethral ethanol ablation of the prostate (TEAP) may be used totreat BPH and typically uses a cystoscope with a curved needle to injectethanol in various doses.

High intensity focused ultrasound (HIFU) may be used to treat BPH andnoninvasively focuses ultrasound waves to heat and destroy targetedprostate tissue.

Various radiofrequency current treatment methods of BPH have beendeveloped. Some methods are shown and described in U.S. Pat. Nos.6,106,521; 6,638,275; and 6,016,452, all herein incorporated byreference in their entireties. In one treatment method, transurethralneedle ablation, a small needle is inserted into the prostate from theurethra. Radio frequency (RF) energy is applied to the needle togenerate heat in specific areas of the prostate. RF frequency basedablation of tissue is done via thermal treatment. Typically, treatmentis done until a certain temperature is reached and is then discontinued.An assumption is made that sufficient ablation has occurred on the basisof the reached temperature.

As may be appreciated, many of these BPH treatment methods includetransurethral access. Transurethral access may involve catheter-basedelectrodes within the prostatic urethra (see, for example, U.S. Pat.Nos. 6,517,534 and 5,529,574) or electrodes designed to puncture theurethra and dwell inside the prostate (see, for example, U.S. Pat. Nos.6,638,275; 6,016,452; 5,800,378; and 5,536,240), transurethral accessincluding balloons for positioning and stabilizing the electrodes (see,for example, U.S. Pat. Nos. 6,517,534 and 7,066,905), transurethralaccess including means for puncturing the urethral wall (see, forexample, U.S. Pat. No. 5,385,544), and transurethral access includingmeans for more accurately placing the electrodes (see, for example, U.S.Pat. No. 6,638,275).

Accordingly, a need exists in the art for a minimally invasive lowpower, non-thermal method of treating tissue via direct currentablation.

BRIEF SUMMARY

Systems and methods for treating tissue, and particularly systems andmethods for non-thermal ablation of tissue, are provided. In variousembodiments, the systems and methods use a non-implantable systememploying direct current ablation for targeting the area to be treated.DC current ablates tissue by imparting extreme pH into the tissuesurrounding the electrode. In general, the systems and methods may beused to treat any form of tissue where ablation is desired including,for example, adipose tissue, muscular tissue, glandular tissue, nodulartissue, and fibrous tissue. In specific embodiments, the systems andmethods may be used to treat benign prostatic hypertrophy or hyperplasia(BPH). In other embodiments, the systems and methods may be used totreat cancerous tissue and benign tumors. One skilled in the art willappreciate that specifics of the systems and methods may be modified foraccess to various sites in the body for treating different tissues.

In one embodiment, a non-implantable minimally invasive system fortreatment of issue in a body via direct current ablation is provided.The system includes a catheter, between 2 and 12 electrodes, a powersource, and a fixation element. The catheter is configured for insertioninto the body such that a portion of the catheter remains outside of thebody when the catheter is in a treatment position proximate the tissueto be treated. The electrodes are positioned for deployment through andoutwardly from the catheter. An active area of at least one electrodedelivers a charge to impart a high pH or a low pH such that a necroticzone is created to form a field of treatment. The power source isconfigured for receiving treatment parameters and applying directcurrent and power to the plurality of electrodes based on the treatmentparameters. The direct current is applied at a magnitude of betweenapproximately 10 and 50 mA per electrode and the power is applied atbetween approximately 20 and 3200 mW of power per electrode to deliverbetween 15 and 90 coulombs of charge per electrode. The fixation elementis operably associated with the catheter for maintaining the catheter ina treatment position during treatment. Ablation of tissue using thesystem is substantially non-thermal.

In another embodiment, a minimally invasive method for treating tissuein a body via direct current ablation is provided. The method includesinserting a catheter into the body, wherein a portion of the catheterremains outside of the body when the catheter is in a treatmentposition, deploying a fixation element associated with the catheter tofix the catheter in the treatment position, and deploying a plurality ofelectrodes through the catheter into the tissue proximate the catheter.The method further includes determining treatment parameters andinputting the treatment parameters into at least one of a power sourceand a processor. A charge is delivered to the electrodes with the powersource by applying between approximately 10 and 100 mA of direct currentand less than 3200 mW of power to deliver a charge to the electrodes.The direct current applied is based on the treatment parameters. Atleast one of a high pH and a low pH is imparted by at least one of theelectrodes upon application of the direct current such that a necroticzone is created. Application of the direct current is substantiallynon-thermal. Application of direct current to the treatment area isstopped once the treatment parameters are reached. The application ofcurrent to the electrodes is done in between approximately 8 and 100minutes with the catheter in a single treatment position.

In a further embodiment, a non-implantable minimally invasive system fortreatment of issue in a body via direct current ablation is provided.The system includes a trans-lumen catheter, between 2 and 12 electrodes,a power source, and a fixation element. The semi-flexible trans-lumencatheter is configured for insertion into the body such that a portionof the catheter remains outside of the body when the catheter is in atreatment position proximate the tissue to be treated. The electrodeshave an insulated portion and an active portion. Each electrode has atotal length of 14 to 22 mm with the active portion having a length ofbetween 3 and 12 mm. The active portion of at least one of theelectrodes delivers a charge to impart a high pH or a low pH such that anecrotic zone is created. The electrodes are positioned for deploymentthrough and outwardly from the catheter at an angle of 15 to 90 degreesfrom a longitudinal axis of the catheter. The power source is configuredfor receiving treatment parameters and applying direct current and powerto the plurality of electrodes based on the input parameters. The directcurrent is applied at a magnitude of between approximately 10 and 50 mAper electrode and the power is applied at between approximately 20 and3200 mW of power per electrode to deliver between 15 and 90 coulombs ofcharge per electrode. The fixation element is operably associated withthe catheter for maintaining the catheter in the treatment positionduring treatment. Ablation of tissue using the system is substantiallynon-thermal.

In one embodiment, a non-implantable minimally invasive system fortreatment of tissue in a body via direct current ablation is provided.The system includes a catheter, a plurality of electrodes positioned fordeployment through the catheter, a power source for applying power tothe plurality of electrodes, and a fixation element operably coupledwith the catheter for maintaining the catheter in a treatment positionduring treatment of the tissue, wherein such treatment is substantiallynon-thermal. The catheter may be a semi-flexible catheter configured forinsertion into the body, wherein a portion of the catheter remainsoutside of the body when the catheter is in a treatment position. Theplurality of electrodes may be provided such that deployment is throughand outward from the catheter. At least one electrode imparts a high pHand at least one electrode imparts a low pH and imparting of the highand low pH by the electrodes creates a necrotic zone around eachelectrode. The necrotic zones coalesce to form a field of treatment. Thepower source applies power to the plurality of electrodes at between 20and 3200 mW.

In another embodiment, a minimally invasive method for treating tissuein a body via direct current ablation is provided. The method includesinserting a catheter into the body such that a portion of the catheterremains outside of the body, deploying a fixation element to fix thecatheter in a treatment position, deploying a plurality of electrodesthrough the catheter, applying power to the plurality of electrodes,using the electrodes to apply a current to the tissue, and removing thecatheter from the body. Inserting the catheter into the body positionsthe catheter in a treatment position wherein a portion of the catheterremains outside of the body. Power is applied to the electrodes atbetween approximately 20 and 3200 mW. The electrodes in turn apply acurrent of between approximately 20 and 40 mA wherein at least oneelectrode imparts a high pH and at least one electrode imparts a low pHupon application of the current such that a necrotic zone is createdaround each of the electrodes and wherein the necrotic zones coalesce toform a field of treatment. Substantially no heat is created during useof the electrodes.

While multiple embodiments are disclosed, still other embodiments of thepresent invention will become apparent to those skilled in the art fromthe following detailed description. As will be apparent, the inventionis capable of modifications in various obvious aspects, all withoutdeparting from the spirit and scope of the present invention.Accordingly, the detailed description is to be regarded as illustrativein nature and not restrictive.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a block anatomy diagram of the prostate area.

FIG. 2a illustrates a system for treating tissue, in accordance with oneembodiment.

FIG. 2b illustrates a system for treating BPH, in accordance with oneembodiment.

FIG. 3a illustrates a side view of an electrode, radius of treatment,and treatment zone, in accordance with one embodiment.

FIG. 3b illustrates an end view of an electrode, radius of treatment,and treatment zone, in accordance with one embodiment.

FIG. 4a illustrates anatomy of a prostate region prior to deployment ofa device for treating tissue.

FIG. 4b illustrates transurethral insertion of a catheter for deploymentof a device for treating tissue, in accordance with one embodiment.

FIG. 4c illustrates deployment of electrodes, in accordance with oneembodiment.

FIG. 5 illustrates a block diagram of a method for treating tissue, inaccordance with one embodiment.

FIG. 6a illustrates a treatment zone for a dose that just touches thecapsule, in accordance with one embodiment.

FIG. 6b illustrates a treatment zone for a dose that is overdosed, inaccordance with one embodiment.

FIG. 7 illustrates a table showing time-temperature relationship for 90%normalized cell death in human BPH tissue from heating.

FIG. 8a illustrates changes to the shape of the treatment zone, inaccordance with various embodiments.

FIG. 8b illustrates coronal tracing of a treatment zone, in accordancewith one embodiment.

FIG. 8c illustrates transverse tracing of a treatment zone, inaccordance with one embodiment.

FIG. 9a illustrates a prostate anatomy with a large median lobe thatextends up in the bladder.

FIG. 9b illustrates positioning of a system for treatment of the medianlobe, in accordance with one embodiment.

FIG. 9c illustrates treatment zones created through treatment of themedian lobe, in accordance with one embodiment.

FIG. 9d illustrates an alternative treatment method for treating themedian lobe, in accordance with one embodiment.

FIG. 10a illustrates a perspective view of a system for median lobetreatment, in accordance with one embodiment.

FIG. 10b illustrates an end view of the catheter of the system of FIG.10 a.

FIG. 11 illustrates overlapping treatment zones, in accordance with oneembodiment.

FIG. 12 illustrates electrodes placed in close proximity, in accordancewith one embodiment.

FIG. 13a illustrates dose delivered versus volume of tissue treated, inaccordance with one embodiment.

FIG. 13b illustrates dose delivered versus expected radius of treatmentfor a 6 mm electrode in prostatic tissue, in accordance with oneembodiment.

FIG. 13c illustrates dose delivered versus expected radius of treatmentfor 12 mm electrode in prostatic tissue, in accordance with oneembodiment.

FIG. 13d illustrates current applied versus dose response, in accordancewith one embodiment.

FIG. 14 illustrates and defines the period and amplitude of currentramping during the start of treatment, in accordance with oneembodiment.

FIG. 15a is an in vivo image illustrating a liquefaction necrosishistology at the boundary of a cathode treatment zone.

FIG. 15b is an in vivo image illustrating a coagulation necrosishistology at the boundary of an anode treatment zone.

FIG. 16 illustrates a view of electrode deployment into pretreatedtissue.

FIG. 17a illustrates a system for tissue treatment including a catheterand electrodes with the electrodes deployed without vacuum, inaccordance with one embodiment.

FIG. 17b illustrates a system for tissue treatment including a catheterand electrodes with the electrodes deployed with vacuum, in accordancewith one embodiment.

FIG. 18 illustrates an embodiment of a system for treating tissueincluding vacuum ports at the electrode holes, in accordance with oneembodiment.

FIG. 19a illustrates balloon deployment in a bladder, in accordance withone embodiment.

FIG. 19b illustrates catheter deployment while applying force towards abladder, in accordance with one embodiment.

FIG. 19c illustrates catheter deployment while applying force away fromthe bladder in accordance with one embodiment.

FIG. 20a illustrates electrode deployment in a prostate, in accordancewith one embodiment.

FIG. 20b illustrates catheter rotation for movement of electrodes, inaccordance with one embodiment.

FIG. 21a illustrates a coronal view of a system comprising two axialplanes of four electrodes each, in accordance with one embodiment.

FIG. 21b illustrates a transverse view of a system comprising fourelectrodes in each axial plane, in accordance with one embodiment.

FIG. 22a illustrates two cathodes in parallel and two anodes in paralleland the associated treatment zones with moderate resistance, inaccordance with one embodiment.

FIG. 22b illustrates an electrical diagram of the embodiment of FIG. 22a.

FIG. 22c illustrates treatment zones with high resistance, in accordancewith one embodiment.

FIG. 23a illustrates an exploded view system for treating tissue, inaccordance with one embodiment.

FIG. 23b illustrates the system of FIG. 23 a.

FIG. 24a illustrates a system for DC ablation with an elongated airlessanchor in a collapsed configuration, in accordance with one embodiment.

FIG. 24b illustrates a system for DC ablation with an elongated airlessanchor in an expanded configuration, in accordance with one embodiment.

FIG. 25 illustrates a system for BPH treatment configured for insertionthrough the urethra until the distal end of the device is in thebladder, in accordance with one embodiment.

FIG. 26a illustrates a coronal view of a system having a forward anglingelectrode array, in accordance with one embodiment.

FIG. 26b illustrates a transverse view of a system having a forwardangling electrode array, in accordance with one embodiment.

FIG. 27 illustrates an 8-electrode array in two rows of four, inaccordance with one embodiment.

FIG. 28 is a block diagram of a generator, in accordance with oneembodiment.

FIG. 29a illustrates a separate battery and DC/DC converter circuitprovided to power each current source, with the batteries electricallyisolated from each other, in accordance with one embodiment.

FIG. 29b illustrates a single power source used for all current sourcesand a transformer based isolation circuit provided for each currentsource, in accordance with one embodiment.

FIG. 30 illustrates a generator with electrode control circuits, inaccordance with one embodiment.

FIG. 31 illustrates a current profile for reducing pain associated withDC ablation, in accordance with one embodiment.

FIG. 32 illustrates TENS-like pulses over a DC voltage, in accordancewith one embodiment.

FIG. 33a illustrates a Therapy Settings screen of a generator display,in accordance with one embodiment.

FIG. 33b illustrates a Therapy Ready screen of a generator display, inaccordance with one embodiment.

FIG. 33c illustrates a Therapy Running screen of a generator display, inaccordance with one embodiment.

FIG. 33d illustrates an Add New Doctor screen of a generator display, inaccordance with one embodiment.

FIG. 33e illustrates a switch and display layout of a generator, inaccordance with one embodiment.

FIG. 34a illustrates a slice of prostate 20 days after treatment, inaccordance with one embodiment.

FIG. 34b illustrates a slide of prostate 40 days after treatment, inaccordance with one embodiment.

FIG. 35 illustrates treatment volume against dose delivered for anodetreatment and cathode treatment for beef rounds, in accordance with oneembodiment.

FIG. 36 illustrates cathode results for treatment volume against dosedelivered for a 20 mA cathode, a 40 mA cathode, and a 60 mA cathode, inaccordance with one embodiment.

FIG. 37a illustrates a nitinol anode before starting a test.

FIG. 37b illustrates the nitinol anode of FIG. 36b after the test wasstopped.

FIG. 38 illustrates results from the first two stages of human prostatetissue study.

FIG. 39 is an in vivo image illustrating the necrosis volume achieved bythe transurethrally ablating tissue with DC ablation.

DETAILED DESCRIPTION

Systems and methods for treating tissue, and particularly systems andmethods for non-thermal ablation of tissue, are provided. In variousembodiments, the systems and methods use a non-implantable systememploying direct current ablation for targeting the area to be treated.DC current ablates tissue by imparting extreme pH into the tissuesurrounding electrode. DC current ablation uses low power to treattissues and creates necrosis without a significant increase in tissuetemperatures. In general, the systems and methods may be used to treatany form of tissue where ablation is desired including, for example,adipose tissue, muscular tissue, glandular tissue, nodular tissue, andfibrous tissue. In specific embodiments, the systems and methods may beused to treat benign prostatic hypertrophy or hyperplasia (BPH). Inother embodiments, the systems and methods may be used to treatcancerous tissue and benign tumors. One skilled in the art willappreciate that specifics of the systems and methods may be modified foraccess to various sites in the body for treating different tissues.

Ablation of pathologic tissue can be performed using low level DCcurrent. This may be done by powering multiple electrodes and impartinga high pH at one polarity electrode and a low pH at the oppositepolarity electrode. Generally, DC ablation resists diffusing acrosstissue boundaries and thus can be used to treat tissue with minimalconcern to affecting adjacent tissues. Further, in systems employing aplurality of electrodes, treatment may be done with relatively slowapplication of DC current with the total treatment time reduced by theplurality of electrodes.

System Overview

FIG. 2a illustrates a basic system configuration. As shown, the system10 includes a generator 12, a catheter 14, electrodes 18, and a cable 16running from the generator 12 to the catheter 14. The catheter 14 may beinserted in the body to a desired location for tissue treatment. Oncepositioned, the electrodes 18 may be deployed, for example through thecatheter 14. To treat tissue, power is provided by the generator 12 tothe electrodes 18. The electrodes then apply a DC current to a treatmentarea of the tissue. The tissue is thus treated by DC ablation in anon-thermal manner.

FIG. 2b illustrates an embodiment of the system of FIG. 2a configuredfor treatment of prostate tissue (or BPH treatment). As shown, thesystem 10 includes a generator 12, a catheter 14, an electricalconnection 16 from the generator to the catheter, a plurality ofelectrodes 18, a mechanism 22 for deploying the electrodes, astabilization mechanism or fixation element 20, and a mechanism 24 fordeploying the stabilization mechanism. In various embodiments, thecatheter 14 may be a transurethral catheter. In some embodiments, theelectrodes 18 may be provided as pairs of electrodes. In someembodiments, an electronic control system may be included. The systemand method may be used for treatment of BPH via deployment of the one ormore electrodes through the transurethral catheter and application ofdirect electrical current to the one or more electrodes. In alternativeembodiments, the system may comprise a catheter for other laparoscopicor percutaneous access to a treatment site. The electrodes produce afield of treatment that covers a predictable area of the target tissue.When deployed transurethrally, the electrodes can produce a field oftreatment covering a predictable area of prostatic tissue. A necroticzone may be created around each of the electrodes and the creatednecrotic zones coalesce to form the field of treatment. The field oftreatment begins at the electrode and diffuses out generally passively.

The electrodes may be provided in any number, may have various shapes,may have various deployment configurations, and may be manufactured ofvarious materials, as shown and discussed in copending U.S. patentapplication Ser. No. ______, herein incorporated by reference in itsentirety. In some embodiments, the electrodes are provided in pairs. Theability to control the mechanical length, angle, and electrical polarityof each electrode, as well as the amount of current passing through eachelectrode allows debulking of a predictable region in a controlledmanner while reducing risk of damage to adjacent, non-targeted areas.Generally, application of DC ablation to treat tissue will not result inscar tissue such as arises from other forms of treatment.

In the embodiment shown in FIG. 2b , the electrodes 18 are provided asfour electrode pairs, each electrode being generally cylindrical. Asshown, two of the electrode pairs comprise shorter electrodes and two ofthe electrode pairs comprise longer electrodes. Each electrode paircomprises an anode and a cathode. An anode is defined as the electrodewith higher voltage potential. A cathode is defined as the electrodewith the lower voltage potential. In the embodiment of FIG. 2b , theelectrodes deploy outward from the catheter. Such outward deployment maybe, for example, radial or may be linear. Generally, the electrodes maybe coupled to the catheter or to a support structure in the catheter. Ascan be appreciated, the electrodes and their coupling with the catheteror a support structure provided within the catheter may be configured toextend from the catheter at different angles, for different lengths,etc. Angles of extension may further be influenced by the shape andconfiguration of the routing holes. The various system configurationsmay be designed based on the tissue to be treated and a selected accessroute to the tissue to be treated. In some embodiments, for example, thesystem may be configured for treatment of prostate tissue, or morespecifically, for treatment of a large region of prostate tissue.

The electrodes 18 are configured for puncture and proper placement ofthe electrode tip to create a desired treatment area. The electrodes 18further are configured to resist corrosion. In some embodiments, theelectrodes 18 may comprise a Nitinol wire with a corrosion resistantcoating. The corrosion resistant coating may be, for example, platinum.In some embodiments, the electrodes may be configured to be atraumatic.In an embodiment comprising needle electrodes, for example, the tip ofthe needle electrode may be self-introducing. Using a transurethralapproach, deployment of the electrodes comprises extension from thetransurethral catheter and through the urethra. Accordingly, theelectrodes pierce the urethra. Thus, in embodiments for treating BPH,the electrode tip may be sufficiently sharp to penetrate the urethra.

In use, current is supplied to the electrodes to create a reactionaround the electrodes to change the structure of the tissue in atreatment zone around the electrodes. The system thus may furtherinclude a generator for supplying current to the electrodes. Thenon-thermal ablation system generally is a lower power system, using,for example, on the order of milliwatts. The system thus does not createsignificant heat during treatment, thus mitigating side effects oftenassociated with thermal treatment. The size and shape of the treatmentzone varies depending on, at least, treatment time, current delivered,electrode size and shape, and positioning of the electrode relative totissue boundaries. As a general matter, by using a plurality ofelectrodes that are properly placed, treatment may be done at arelatively slow rate but the total treatment time may be relativelyfast. The shape of the treatment zone around a cylindrical electrode,such as shown in FIG. 2b , is approximately an ellipsoid or cylinderwith hemispheric ends with the distance from the boundary of thetreatment zone and the surface of the electrode having a generallyconsistent radius, referred to herein as the radius of treatment.

FIG. 3a illustrates a side view and FIG. 3b illustrates an end view ofan active electrode. As shown, the electrode 31 includes an activeportion 32 and an insulated portion 36. The insulated portion 36 of theelectrode is resistant to the corrosive environment created duringablation. FIGS. 3a and 3b further illustrate the radius of treatment 34,treatment zone 30 associated with the active portion 32 of the electrode31.

FIGS. 4a-4c illustrate deployment of a device for treating tissue in aprostate region, in accordance with one embodiment. Specifically, FIG.4a-4c illustrate the device relative the urethra 40, prostate gland 41,prostate capsule or wall 50, and bladder 42. Before treatment, thetissue to be treated may be assessed to determine appropriate treatmentprotocol. FIG. 4a illustrates a simplified diagram of the anatomy of aprostate region prior to deployment of a device for treating tissue.FIG. 4b illustrates transurethral insertion of the catheter 44 and showsthe distal end 43 of the catheter 44. FIG. 4c illustrates deployment ofthe electrodes 48 and their insulation sleeves 49 through the catheter44; with the catheter 44 generally fixed in place by one or moreballoons 46, 47 (or other fixation element).

FIG. 4b illustrates an embodiment for BPH treatment wherein a catheter44 is inserted transurethrally. In various embodiments, the catheter 44may be flexible or semi-flexible or semi-rigid distally from theentrance of the urethra, as deployed. In one embodiment the catheterbody has a flex modulus of between about 0.4 and 3 GPa. The catheter maybe advanced with the guidance of a trans-rectal ultrasound (TRUS). InFIG. 4b , the distal end 43 of the catheter 44 is shown inserted in thebladder 42. The catheter 44 may include one or more balloons 46 and 47,as shown in FIG. 4c . To fix the system in place, one balloon 46 isexpanded within the bladder and one balloon 47 is expanded in theurethra 40. Other anchoring mechanisms or fixation elements mayalternatively be used. In some embodiments, the balloon 46 expandedwithin the bladder 42 assists in placement of the catheter 44. Forexample, the balloon 46 may be inflated after the catheter tip hasentered the bladder and the catheter may be retracted until resistanceis felt by the balloon 46. The balloons further may assist inmaintaining the catheter in a treatment position. Various methods ofimaging, such as ultrasound using a rectal probe, may be used to helpposition the catheter.

FIG. 4c illustrates electrode deployment after anchoring of thecatheter. In the embodiment of FIG. 4c , the catheter 44 includes eightneedle electrodes 48 at four different positions on the catheter 44. Theelectrodes 48 and their electrical insulation sleeves 49 pierce theurethra 40 and enter the prostate 41. As shown, the length of theelectrodes 48 may be varied to optimize the field of treatment for thegiven size and shape of the prostate 41. In the deployment position,none of the electrodes 48 pierce the prostate wall 50. After theelectrodes have been positioned, current is applied to create acidic andbasic zones and thus ablate tissue in the treatment zone. In embodimentscomprising eight electrodes, the system may be used to create eightnecrotic zones in a single deployment. Thus, the treatment may beperformed with a single deployment, employing relatively slow treatmentwith respect to application of current but having relatively fasttreatment time because all treatment zones may be formed substantiallysimultaneously. This decreases physician time and burden to deliver thetreatment to patients.

In some embodiments for treatment of BPH, the cathode may be placedproximate the bladder neck or base of the prostate. A cathode so placedcreates a large area of necrosis with less relative variation. Becauseof the edemic reaction at the cathode, the healing response andresorption of tissue into the body (and associated relief of symptomaticBPH) is accelerated. The area closest to the bladder neck in theprostate is responsible for the greatest contribution to lower urinarytract symptoms due to BPH. The anode may be placed closer to theverumontanum or as an indifferent electrode. Another embodiment includesplacing the cathodes in the lateral posterior quadrant of the tissuerelative to the urethra and placing the anodes in the lateral or lateralanterior quadrant of the tissue relative to the urethra. A treatmentzone forms around each of the electrodes and diffuses out generallypassively. Thus, the electrodes may be placed in the tissue relative toeach other such that the treatment zones overlap and coalesce. In oneembodiment an indifferent electrode is used as either the anode orcathode in addition to the electrodes in the catheter which create thetreatment zones. The indifferent electrode can be a patch electrode thatmakes contact with the skin of the patient. In one embodiment the patchis placed on the buttocks of the patient. The indifferent electrode mayhave a substantially large surface area to reduce the electrochemicalaffect on the skin. In one embodiment indifferent electrode incorporatesa flushing system to maintain a neutral pH at the surface of theskin-electrode interface.

Method of Treatment

FIG. 5 illustrates a block diagram of a method 100 for treating tissue.In the embodiment shown, the method comprises assessing and measuringthe prostate or other tissue to be treated [block 102], determiningdosage levels [block 104], application of an anesthetic [block 105],inserting a catheter [block 106] and fixing the position of the catheterwith a fixation element [block 107], deploying electrodes via thecatheter[block 108], applying current to the electrodes to create acidicand basic treatment zones [block 110], cell necrosis [block 112],withdrawal of the electrodes [block 114], and withdrawal of the catheter[block 116]. It is to be appreciated that, in some embodiments, not allof these steps may be performed and/or additional steps may beperformed. Further, in some embodiments, one or more of the steps may beperformed in a manner other than specifically disclosed herein.

In treatment of BPH, prostate size may vary considerably and selectionof appropriate number and size of electrodes to deploy may vary based onsize of the prostate. Generally, using systems and methods such asdisclosed herein, a minimum of 4 electrodes will be deployed. In someembodiments, eight electrodes, with eight associated treatment zones areprovided and deployed in a single deployment. To evaluate the number andsize of electrodes for deployment and/or dosage levels, it may bedesirable to examine the patient to determine size of the tissue area tobe treated. Such examination may be visual, tactile, or other. In oneembodiment, examination may be done using a cystoscope, a tubularinstrument used to visually examine the interior of the urinary bladderand urethra. In various embodiments, the location for electrodedeployment may be determined by estimating the size and shape of theprostate through cystoscopy and/or transrectal ultrasound (TRUS) and/orother suitable imaging method. Other options include CT, MRI, PET, orX-ray. Treatment zone size may also be determined to minimizeinteraction with the prostate capsule and the prostatic urethra.Minimizing treatment interactions with the capsule and prostatic urethrawill reduce the amount of irritative urinary symptoms after treatment.An appropriate system configuration thus may be selected based on theprostate size to be treated to minimize these interactions. Dosagelevels may be determined based on the assessed treatment area. Thedesired treatment area can be determined by measuring the overallprostate dimension such as transverse width, sagittal length, andanterior to posterior height. Generally, the most important anatomicaldimension to determine treatment may be the prostate transverse width.Diffusion through tissue is typically predictable, thus facilitatingdosage setting.

In one embodiment the generator is configured to display the predictedareas of necrosis over an uploaded image from ultrasound. In otherembodiments, other imaging devices may be used to provide such imagery.The size and shape of the treatment zone varies with the charge settinginputted into the generator. In some embodiments the generator isconfigured to communicate with an ultrasound machine overlaying thepredicted treatment zone on the ultrasound image. In embodiments whereinthe system is used for treatment of prostate, imaging may be used priorto insertion of the system. Such imaging may be, for example, a rectalultrasound whereby the prostate is measured. Measurements of theprostate may then be compared to a table to determine appropriate lengthof insertion and dose for treatment.

Block 104 of FIG. 5 may include entry of input treatment parameters intothe generator. In some embodiments, the generator may include switches,keys or buttons for the entry of one or more input treatment parametersby the user of the system and those input treatment parameters may beused by the generator to control the delivery of current. Duringtreatment, the generator may compare measured treatment parameters withinput treatment parameters to determine when to pause or stop thetreatment. In one embodiment, the input treatment parameter may be dose(charge) in coulombs. During treatment, the generator stops treatmentwhen the measured charge is greater than or equal to the charge enteredby the user. In another embodiment, input treatment parameters may becurrent level and time. During treatment, the generator may stoptreatment when the measured charge is greater than or equal to theproduct of the current level and time input parameters. In anotherembodiment, the input treatment parameter may be current level. Duringtreatment, the generator may pause or stop treatment if the measuredcurrent level exceeds the current level input parameter. In anotherembodiment, the input treatment parameter may be time with apredetermined current level.

The following look-up tables can be a guide for determining the chargeto be delivered and the length of insertion of the electrodes intoprostates with varying transverse widths to optimize treatment.

Table 1 shows optimized treatment settings for a catheter which haselectrodes that extend outward from the catheter generally perpendicularfrom the catheter body (Extension angle between 60 and 120 degrees) (Theactive length of the electrode is assumed to be 6 to 8 mm in thistable):

TABLE 1 Expected Treatment Prostate Zone Radius Electrode TransverseDose or around each Extension Width (mm) Charge (C) electrode (mm)Length (mm) 30-40 36-48 5-7 13 40-50 40-52 6-8 16 >50 48-60 7-9 20

Table 2 shows optimized treatment setting for a catheter which haselectrodes that extend outward from the catheter towards the cathetertip with an extension angle of 45 degrees to 30 degrees. The activelength of the electrode is assumed to be 6 to 8 mm in this table:

TABLE 2 Distal Electrode Expected Prostate Insertion Point Optimal DoseTreatment Electrode Transverse from Fixation or Charge Zone RadiusExtension Width Element in (C) per around each Length (mm) Bladder (mm)electrode electrode (mm) (mm) >30 14-16 28-36 4-6 16 >30 16-18 36-48 5-718 >35 18-20 36-48 5-7 20 >40 20-22 48-60 7-9 22

Table 3 shows optimized treatment setting for a catheter which haselectrodes that extend outward from the catheter towards the cathetertip with an extension angle of 60 degrees to 45 degrees. The activelength of the electrode is assumed to be 6 to 8 mm in this table:

TABLE 3 Distal Electrode Optimal Expected Insertion Point Dose orTreatment Electrode Prostate from Fixation Charge Zone Radius ExtensionTransverse Element in (C) per around each Length Width (mm) Bladder (mm)electrode electrode (mm) (mm) >30 12-14 28-36 4-6 16 >35 14-16 36-48 5-718 >40 15-17 36-48 5-7 20 >45 16-18 48-60 7-9 22

Table 4 shows optimized treatment setting for a catheter which haselectrodes that extend outward from the catheter towards the cathetertip with an extension angle of 30 degrees to 15 degrees. The activelength of the electrode is assumed to be 6 to 8 mm in this table:

TABLE 4 Distal Electrode Expected Prostate Insertion Point Optimal DoseTreatment Electrode Transverse from Fixation or Charge Zone RadiusExtension Width Element in (C) per around each Length (mm) Bladder (mm)electrode electrode (mm) (mm) >30 16-18 20-28 3-5 16 >30 18-20 24-32 4-518 >30 20-22 28-36 4-6 20 >30 22-24 28-36 4-6 22

To determine how many electrodes should be used to treat a prostate acystoscopy should be done to measure the distance between the bladderneck and the verumontanum. If the measurement is less than 2.5 cm thepatient is not well suited to be treated with a catheter that haselectrodes that angle away from the catheter of less than 60 degreesupon electrode extension (extension angle). Table 5 shows the number ofelectrodes that should be used in treating prostates with varyingdistances between the bladder neck and verumontanum with catheters withdifferent extension angles. This assumes that 4 electrodes are placed ineach plane along the urethra and each plane is spaced between 6 and 12mm.

TABLE 5 # of Cystoscopy Optimal # of Electrodes in MeasurementElectrodes in # of Electrodes in # of Electrodes in catheter withbetween bladder catheter with catheter with catheter with extension neckand extension angle extension angle extension angle angle verumontanumbetween 90 and between 60 and 45 between 45 and between 30 (cm) 60degrees degrees 30 degrees and 15 degrees >2.5 4 NA NA NA 2.5-4.5 8 4 44 >4.5 12 8 8 4

In some embodiments, the prostate capsule may be used as a safety marginto deliver DC ablation to the periphery zone of the prostate. Because ofthe capsule around the prostate and the creation of ions using DCablation, the prostate can be overdosed to effectively treat theperiphery zone, especially for applications for treating canceroustissue. This overdose may range from approximately 160% to approximately260% of the dose for allowing the ionic gradient to reach the prostatecapsule. FIGS. 6a and 6b illustrate treatment zones for a dose that justtouches the capsule (FIG. 6a ) and a dose that is overdosed (FIG. 6b ).A cancer is shown in each of the figures with the treatment radius ofeach electrode being suitable for treating the cancer. Each of FIGS. 6aand 6b show the same electrode placement. Dose typically may bedetermined assuming a radius that reaches the capsule but does notextend past the capsule, radius r shown in FIG. 6a . The dose may beincreased to effectively increase radius but the radius r towards thecapsule will not extend past the capsule because of the anatomy of thecapsule. Thus, as shown in FIG. 6b , radius r towards the capsuleremains the same but radius R away from the capsule increases. In oneembodiment, the treatment radius in FIG. 6a is achieved using a dose of30 C and results in a radius r of 6 mm. In one embodiment, the treatmentradius R in FIG. 6b is achieved using a dose of 78 C and results in aradius R of 10 mm. An algorithm may be developed using routineexperimentation for current and charge balancing to produce the desiredtreatment zone.

In some embodiments, the area for treatment may be prepared fortreatment, as shown and discussed in copending U.S. patent applicationSer. No. ______, herein incorporated by reference in its entirety.Unlike many ablation methods, DC ablation does not use extremes oftemperature to cause necrosis and therefore can be used safely adjacentvascular structures.

In some embodiments, a saline solution or saline gel may be introducedto provide additional safety margin where ablation of tissue is notdesired. In some embodiments, a saline solution with a pH of 7 may beprovided adjacent to a treatment area. This substantially prevents theacidic and basic treatment zones from advancing into that area. Theneutral pH of the saline dilutes the advancing acidic and basic gradientto a point which does not create necrosis in the tissue in irrigatedareas. The saline solution may be delivered to an area by any suitablemethod. For example, in a first embodiment, saline may be introducedinto a body lumen where preservation is desired, such as the urethra,through the therapy delivery catheter or through a separate dedicatedirrigation catheter. In a second embodiment, saline may be injectedthrough a needle into a capsule to preserve a certain region within thecapsule. In a third embodiment, saline may be injected into a bodycavity adjacent to the capsule of the body being treated to preserveadjacent tissue, such as the rectum. Saline saturation of the treatmentarea may further be done if a concern for dehydration arises. In otherembodiments, distilled water may be used as an alternative to salinesolution. As discussed with respect to application of current to theelectrodes, muscle contractions may arise during treatment. Generally,muscle contractions are undesirable during treatment. A nerve block maybe used in some embodiments to minimize patient discomfort duringtreatment. In some embodiments, anesthetic may be applied. It is to beappreciated, however, that the system and method disclosed herein aresignificantly more tolerable to patients than previous methods of BPHtreatment and may be performed with minimal anesthetic. For example, themethods disclosed herein may be performed with the patient conscious.

Pain management during treatment according to the systems and methodsprovided herein may be done by local anesthesia. For example, in someembodiments application of anesthesia may comprise introducing a topicalanesthetic gel (e.g. lidocaine) into the urethra. This may be done, forexample, by injecting into the urethra or coating a catheter that wouldbe inserted and removed prior to inserting the treatment catheter. Thus,in various treatment applications, anesthetic gel may be applied to atransperineal, transrectal, or transurethral catheter for delivery tothe prostate or other tissue. In other embodiments, a nerve block may beinjected locally or a sedative may be orally ingested or intravenouslydelivered.

In some embodiments, the method may include visualization, for exampleto facilitate placement and positioning of the system. Accordingly,visualization elements may be provided as part of the system.Particularly in systems employing a plurality of electrodes, such aseight electrodes, correct positioning can impact results. Thepositioning of the system impacts positioning of all electrodes and,thus, positioning of all necrotic zones. Accurate placement oftransurethral catheters can be optimized with the use of a transrectalultrasound. Ultrasound imaging may be optimized by designing thecatheter or other portion of the system for imaging. The ability toimage the system as the system is placed can enhance results and improvesafety.

Magnetic resonance imaging may alternatively be used to verify positionand treatment for the system for treating tissue as provided herein. Inaccordance with one method, the catheter is placed and the electrodesare inserted. The patient is positioned for MRI imaging and DC ablationis activated at low levels. MRI is performed, tuned to measure theelectromagnetic field of DC current, and therapy is paused. The positionof electrodes and treatment region are verified through examination ofthe MM image. Generally, the imaging sequence may include electricalcurrents, via induced magnetic field, or H⁺ concentration, such as forconventional MRI images, or other sequences such as known to thoseskilled in the art.

Angular orientation of the catheter and electrode array can be verifiedby a physical marker on the body of the catheter or handle that isexposed outside the body. In certain embodiments, this may be a linearmarking or a bubble indicator. Such indicator may also be internal tothe body and may be seen through imaging such as ultrasound, MRI, CT, orX-Ray

The system may be deployed by inserting a catheter proximate the tissueto be treated such that the treatment zone of an electrode deployed fromthe catheter overlaps the tissue to be treated. The catheter may have ahandle provided at a proximal end thereof for handling by a physician,such as a surgeon or urologist. The catheter is inserted until locationof the electrodes, as determined with respect to the catheter, is at thedesired tissue for treatment. Thus, for example for BPH treatment, thecatheter may be inserted into the urethra through the penis untillocation of the electrodes is in the urethra proximate the prostate. Insome embodiments, the catheter may include an anchor for anchoring thecatheter in place during treatment. For example, a pair of pneumaticallyor hydraulically activated balloons may be used to anchor the catheter.

After anchoring (if done) and placement confirmation, the electrodes maybe deployed from the catheter. Electrode deployment may be linear,rotational, or a hybrid of linear and rotational. Deployment of theelectrodes may be triggered, for example, using a push button trigger, aslide mechanism, or other on the catheter handle. In some embodiments,the catheter may be partially retracted or advanced to expose electrodesprovided on a support structure within the catheter. In someembodiments, the electrodes may be deployed through routing holesprovided in an outer sheath or sleeve of the catheter. The electrodesmay extend generally outwardly from the catheter to enter the tissue tobe treated. The position of the electrodes in the tissue affects thetreatment zone. More particularly, the treatment zone generallysurrounds the electrodes

In some embodiments, the inserted length of all deployed electrodes maybe approximately equivalent. This permits the electrodes to be deployedwith a single simple mechanism. In other embodiments, multiple insertionlengths may be used. Such varied insertion lengths may be achieved, forexample, with multiple insertion mechanisms or various cam and/orgearing mechanisms. Treatment zones around each electrode may be thesame size or may vary one to another. The amount of charge to eachelectrode may be controlled to influence treatment zones. For example,where varying sizes of treatment zones are desired and each electrodehas the same length, different currents may be supplied to theelectrodes from independent current sources. Further, in someembodiments, portions of the electrode may be insulated, for exampleportions closest to the catheter to increase the distance from theactive area of the electrode to a structure that is wished to bepreserved, for example the urethra. This facilitates preservation of theurethra to minimize post-procedural irritative symptoms such as dysuria,hematuria, and urinary urgency.

After the electrodes have been positioned, current is applied to createacidic and basic zones. Specifically, direct electrical current isapplied to the electrodes. In some embodiments, the direct electricalcurrent is applied simultaneously to all electrodes from isolatedcurrent sources having individually selectable polarity and chargedelivery. The applied current creates an acidic zone around the anodeand an alkaline or basic zone around the cathode. Generally, thetreatment zone tends to follow, and not cross, a tissue plane.Accordingly, using DC ablation, treatment may be up to the tissue plane.The sizes of the necrotic zones are based on the amount of chargedelivered to each electrode, where charge (coulombs) equals current(amperes) multiplied by time (seconds). In some embodiments, the appliedcurrent is at a relatively low level such as between approximately 1 mAand approximately 100 mA. Generally, treatment time increases as currentdecreases. Treatment time decreases as the number of electrodesincreases. Treatment time may decrease if impedance decreases and thevoltage compliance of the constant current system is low or the systemutilizes constant voltage. In accordance with one embodiment, BPHtreatment is achieved in approximately 30 minutes when using a 4, 6, 8,or 12 electrode array at 20 mA to deliver the treatment of 36 coulombsper electrode pair. Treatment time is reduced to 24 minutes when thecurrent is increased to 25 mA and delivering 36 coulombs per electrodepair. The systems and methods disclosed herein employ slow, low current,low power treatment. Because of the plurality of electrodes and thesubstantially simultaneous treatment through all electrodes, totaltreatment time is nevertheless kept low. Table 6 shows the relationshipsbetween current, power, time, charge, and number of electrodes.

TABLE 6 Charge per Number Total Imped- Time Electrode of Charge Currentance Power (min- Pair Electrode (cou- (mA) (ohms) (mW) utes) (coulombs)Pairs lombs) 10 400 40 30 18 1 18 10 700 70 30 18 2 36 10 1000 100 30 183 54 25 400 250 30 45 1 45 25 700 437.5 30 45 2 90 25 1000 625 30 45 3135 50 400 1000 30 90 1 90 50 700 1750 30 90 2 180 50 1000 2500 30 90 3270

The power applied to the electrodes is low compared to prior methods fortreating BPH. More specifically, the power applied in accordance withsystems and methods disclosed herein is on the order of milliwatts inthe range of 20 to 3200 mW of power per electrode pair. The powertypically used for each electrode pair is between approximately 190 mW(25 mA into a 300 ohm tissue impedance) to 1600 mW (40 mA into a 1000ohm tissue impedance). A common impedance level seen in tissue is 400ohms, and treating with 50 mA equates to a required power output of 1000mW. This low power of treatment delivery allows for insignificant heattransfer to occur between the device and body tissues. This reduces oreliminates pain and discomfort from the heating of surrounding tissuesduring treatment that are experienced with thermal technologiesutilizing significantly higher power. It also reduces or eliminatesscarring and long healing times associated with a thermal wound. RF andmicrowave technologies using thermal energies to create necrosis in softtissue often have power ranges between 15 and 75 W. The amount of powerdelivered by a thermal ablation system is not based directly on themeasurement of the power delivered, but is based on the temperaturemeasurement resulting from the power delivered. In contrast, the amountof charge delivered by the DC ablation system is based directly on themeasurement of the charge delivered, allowing for more precise controlof the size of the necrotic zones.

In order to create substantial cell death a temperature of at least 45degrees C. or an 8 degree increase in tissue temperature must bemaintained for approximately one hour. Substantial cell death occursover 10 minutes at 55 degrees C. FIG. 7 illustrates the relationshipbetween time and temperature. More specifically, FIG. 7 illustrates thetime-temperature relationship for 90% normalized cell death in human BPHtissue from heating. At greater than 100 degrees C. the water present inthe tissue boils and can cause impedance increases such that thermaltherapy becomes intermittent. RF thermal ablation devices attempt tocreate tissue temperatures approaching 100 degrees C. to create necrosiswith minimal treatment time. RF thermal ablation treatments can lastbetween 1.5 and 5 minutes.

DC ablation applied with up to 50 mA only results in a maximum increaseof 4 to 5 degrees C. in the tissues surrounding the electrodes. Lowercurrents will cause a lesser change in tissue temperature in the rangeof 0 to 3 degrees C. This mild increase in temperature does not createnecrosis or act as a mechanism in ablating the tissue over the durationof the DC ablation treatment. These calculations are dependent on tissuetype and vascularization of the tissue.

Inducing high localized temperatures causes surrounding tissues to alsosubstantially increase in temperature. This may lead to collateraldamage of structures outside of the intended treatment area such as, inthe case of BPH treatment, the erectile nerves, rectum, or externalsphincter. Devices that use radiated energy to heat tissues such asmicrowave require a rectal temperature probe to ensure that the rectumdoes not exceed an unsafe temperature. The high temperatures surroundingthe treatment area also leads to a burning sensation in the pelvicregion. Generally at 45 degrees a heat sensation is perceived. This isexceeded at the prostate capsule during thermal ablation treatments. Anon-thermal DC ablation system, such as disclosed herein, does not haveeither of these concerns due to the low power that is delivered.

A single treatment can be done with no repositioning of the catheter andcan be completed in no less than 8 minutes assuming delivering 24 C perelectrode at the rate of 50 mA. A single treatment with no catheterrepositioning can take as long as 100 minutes assuming delivering 60 Cper electrode at a rate of 10 mA. It should be appreciated that,generally, no single treatment should last longer than 45 minutes forpatient comfort and physician burden. Thus a treatment of 60 C should becompleted at a minimal rate of 22 mA. If more treatment is required thecatheter may be repositioned and a second treatment started.

In some embodiments, the electrodes may be generally cylindrical. Theshape of the treatment zone for a cylindrical electrode is a cylinderwith hemispheric ends and approximates an ellipsoid. By adjusting theelectrode length and/or charge delivered, the shape of the ellipsoid canbe controlled to make shapes that are cylindrical, oval, or spherical.As current is applied to the electrodes, an ellipsoid treatment zoneforms around each electrode. The length of the ellipsoid isapproximately equal to the length of the exposed electrode plus thediameter of the treatment zone. If the electrode length is significantlylonger than the diameter of the treatment zone, the shape of the zonewill be nearly cylindrical. The ends will be round (hemispheres) but theshape will be long and narrow like a cylinder. As the treatmentcontinues, the diameter and length of the zone grow. As a percentage ofthe previous dimension, the diameter grows faster than the length. Asthis continues, the shape of the treatment zone becomes more oval thancylindrical and eventually becomes nearly spherical.

FIG. 8a illustrates a treatment zone around an electrode 60 wherein thetreatment zone is, for the purposes of illustration, divided into 4zones 61, 62, 63, and 64, extending radially outward from the electrode60. As shown, the treatment zones 61, 62, 63, and 64 change shape asthey extend away from the electrode 60. The zone 61 closest to theelectrode is nearly cylindrical while the zone 64 farthest from theelectrode is nearly spherical. Accordingly, with electrodes of equallength, treatment zone size as well as shape may vary with differentapplied currents when treating for an equal amount of time. Treatmentshape will vary as well due to the proximity of tissue planes thatimpede the diffusion of the treatment.

FIGS. 8b and 8c illustrate a suitable area to create necrosis in theprostate to relieve symptomatic BPH. FIG. 8b illustrates coronal tracingof a treatment zone. FIG. 8c illustrates transverse tracing of atreatment zone. As shown, the treatment zones 70 may be in the laterallobes 72 of the prostate adjacent to the bladder neck 74 and along theurethra 76 to the verumontanum 78. FIG. 8b also illustrates the bladder71 for reference. Treating in the treatment zones 70 maximizes symptomrelief obtained by treatment as the necrotic tissue is reabsorbed by thebody and pressure is removed from the urethra. The urethral interactionof the treatment may be minimized to reduce transient irritativesymptoms such as hematuria, dysuria, and urinary urgency. Amount ofcharge delivered, electrode shape and size, electrode array, electrodepositioning, number of electrodes, current level, and electrodeinsertion length are all factors in treatment.

In another embodiment the electrodes may be staggered such that they donot align. In another embodiment 3, 5, 6, 7, 9, 10, 11, and 12 electrodearrays may be utilized to treat the prostate with DC ablation throughthe urethra and into the lateral lobes of the prostate. Theseembodiments are optimized to created treatment zones as prescribed inFIGS. 8b and 8 c.

In some patients it may be desirable to treat the median lobe of theprostate instead or in addition to the lateral lobes. FIGS. 9a-9dillustrate median lobe treatment. FIG. 9a shows a prostate anatomy 704with a large median lobe 702 which extends up into the bladder 700. Alarge median lobe 702 can cause a urinary obstruction of the prostaticurethra 706 at the bladder neck 708. Ablating the median lobe can beaccomplished using DC ablation by using a modified method and system fortreating the lateral lobes as previously described.

FIG. 9b illustrates positioning of a system for treatment of the medianlobe. FIG. 9c illustrates treatment zones created through suchtreatment. Treating the median lobe of the prostate can be accomplishedusing methods described herein. As a preliminary matter, it may beuseful to assess the size and position of the median lobe throughvisualization of the median lobe through Ultrasound, CT, MRI orcystoscopy. A transurethral delivery catheter 714 is routed in proximityto the bladder neck 708 and the area to treat identified by inserting acystoscope 710 through or adjacent to the delivery catheter. A pluralityof electrodes 712, for example between 2 and 4 electrodes, may then beextended into the median lobe under cystoscopy guidance. Insertion maybe done either through the urethra near the bladder neck or from thebladder back into the median lobe. After the electrodes are placed adose or charge of 15 to 60 coulombs per electrode may be deliveredcreating treatment zones 716 in the median lobe as shown in FIG. 9c .The catheter may be anchored to prevent the electrodes from movingduring treatment. After treatment is completed the catheter andcystoscope is removed from the body.

FIG. 9d illustrates an alternative treatment method for treating themedian lobe. As shown, the delivery catheter 714 may be routed into thebladder 700 and then curved back towards the median lobe 702 where theelectrodes may be inserted under guidance from a cystoscope.

As may be appreciated by those skilled in the art, similar systems andmethods may be used for ablation of tissue in several different areas ofthe body. Such areas may include, for example, the trachea, stomach,esophagus, rectum, colon, intestine, bladder, uterus, and other tissuesaccessible from a lumen.

FIGS. 10a and 10b illustrate a specific embodiment of the deliverycatheter for a system for treating the median lobe. FIG. 10a illustratesa perspective view and FIG. 10b illustrates an end view. As shown, thesystem may include a semi-flexible catheter 720 and a plurality ofelectrodes 722 positioned for extension from the distal tip of thecatheter. In some embodiments, between 2 and 4 electrodes may beprovided. A cystoscope 724 may be routed down the center of an openlumen 721 of the delivery catheter. The electrodes 722 may be actuatedby a mechanism 726 which remains outside of the body during treatment.The delivery catheter is connected to a generator 728 by an extensioncable 730. The same generator can be used in the median lobe system asthe system for treating the lateral lobes previously described.

In some embodiments, the gas generation and diffusion through tissue canbe used to mark the necrotic region. By calibrating current and time totissue type, the treatment zone (or area of necrosis) can be visualizedon ultrasound. As discussed, the gas created during DC ablation diffusesthrough tissue being treated until it becomes absorbed in solution withthe fluids present in the tissue. By controlling the rate of therapy(current) and the total therapy delivered, the region of gas bubbles inthe tissue can be correlated to the area of necrosis. Such visualizationmay be used, for example, when DC ablation is used to treat benign andmalignant tumors.

In some embodiments, one anode and one cathode are provided per currentsource. This may facilitate control of the treatment zone size. In otherembodiments, more than one anode and one cathode are provided percurrent source. This may reduce the likelihood of poor tissue contactduring treatment. If more than 2 electrodes are used per current source,current may be directed to specific electrodes of the same polarity bymaking some electrodes have higher (or lower) impedance than others.This may be accomplished by varying configurations of the electrodes,for example by creating different surface textures on differentelectrodes, by providing a means for venting gases via some electrodesbut not others, etc.

In various embodiments, size of treatment zone may be customized forspecific treatment positions of the electrodes. For example, intreatment of BPH, smaller treatment zones may be formed near theprostate base and apex and larger zones may be formed in bulkier areas.Such varied treatment zone sizes may be provided by using differentelectrode sizes, differing numbers of electrodes, differing current orcharge delivery, or by varying other process or system parameters. Forexample, shorter electrodes may be used at the distal and proximal endsand longer electrodes may be used in the middle band(s), as shown in theembodiment of FIG. 4c . In an alternative embodiment, fewer electrodescan be used at distal and proximal ends and more electrodes in themiddle band(s). In a further embodiment, less charge may be delivered toelectrodes at distal and proximal ends and more charge may be deliveredto electrodes in middle band(s). In yet a further embodiment, theelectrodes at distal and proximal ends may be programmed as anodes andthose in the middle band(s) as cathodes.

DC current ablates tissue by imparting extreme pH (<5 or >9 to 10) intothe tissue surrounding the electrode. The area surrounding the electrodeaffected by the extreme pH is referred to as the treatment zone. In someembodiments, the system may be deployed to provide overlapping polaritytreatment zones. Such overlapping may optimize the radius of thetreatment zone for tissue ablation. When DC ablation electrodes areplaced in close proximity, the extreme pH zones grow. When they overlapfor a paired electrode, the zones increase in radius more readily thanwhen separate for a given dose.

FIG. 11 illustrates a radius of a combined treatment zone at the pHinterface. The treatment zone may increase approximately 10-20% inradius. Specifically, FIG. 11 illustrates a first electrode 70 with afirst pH extreme 72, a second electrode 74 with a second pH extreme 76,and a typical treatment radius 78. FIG. 11 further illustrates theincreased radius 79 of the combined treatment zone (shown by the dottedline).

Similarly, in other embodiments, the anode and cathode may be placedproximate one another. By placing the anode and cathode (oppositepolarity electrodes) in close proximity to one another, extreme pHs canbe achieved to necrose tissue. The opposite pH levels help to neutralizeone another to decrease the amount of time it takes for the surroundingtissue to return to normal conditions.

FIG. 12 illustrates an embodiment with two anodes 80 and two cathodes82. In one treatment area 83, an anode 80 is placed proximate a cathode82, for example spaced between approximately 2 and approximately 20 mmfrom one another. The same set up is provided in a second treatment area86—an anode 80 placed proximate a cathode 82. As a result, in eachtreatment area 83 and 86, a high pH zone 88 and a low pH zone 89 eacharise proximate to the other. The zones 88 and 89 likely overlap oneanother. In the area of zone overlap, the pH of the tissue can return tonormal within, for example, hours of the DC ablation procedure.

FIGS. 13a through 13d illustrate various effects and relationships ofdosage. FIG. 13a illustrates the dose delivered versus the volume oftissue treated. FIG. 13b illustrates the dose delivered versus the upperand lower limit of expected radius of treatment for a 6 mm electrode inprostatic tissue. FIG. 13c illustrates the dose delivered versus theupper and lower limit of expected radius of treatment for a 12 mmelectrode in prostatic tissue. FIG. 13d illustrates current appliedversus dose response.

Generally, DC ablation creates necrosis around a singular anode and asingular cathode at a rate of approximately 0.07-0.05 cc/C at the anodeand at a rate of approximately 0.10-0.08 cc/C at the cathode. A typicalperiod for treating BPH using systems and methods for DC ablation asdisclosed herein is under 30 minutes. Dosing at approximately 25 mA forapproximately 30 minutes will deliver 45 C. This in turn treats betweenapproximately 5.8 cc and approximately 7.7 cc of tissue per pair ofelectrodes. To achieve a more efficacious treatment, multiple electrodepairs may be used. In some embodiments, 2 to 6 pairs of electrodes maybe used. This correlates to approximately 11.6 to approximately 14.4 ccof treated tissue for 2 pairs of electrodes and between approximately34.8 and approximately 43.3 cc of treated tissue for 6 pairs ofelectrodes. These numbers do not account for the overlap of treatmentzones which decrease the amount of treated tissue. In some embodiments,the treatment zones overlap. Treatment times may vary between 15 and 45minutes depending on the dosing required and rate at which the treatmentis delivered. Alternatively fewer pairs of electrodes could be used in adevice to achieve these same larger treatment zones if the catheter orelectrodes are repositioned between treatments.

The rate at which the charge is applied (current, units of milliamperes)does not affect the ultimate radius of the treatment zone as long as thecurrent provides more charge than the tissue's natural ability tostabilize its own pH. The relationship between current applied and thedose response is shown FIG. 13d . As shown, in some embodiments, it maybe desirable for the treatment current to be at or above approximately 1mA. In the example of FIG. 13d , all currents above 5 mA exhibitgenerally the same dose response. While higher currents may not increasedose response, higher currents may reduce treatment time to deliver thedesired dosage. The higher current, however, may increase likelihood ofpatient discomfort. Generally, as current decreases, patient discomfortand muscle contractions (or muscle twitch) decrease. In someembodiments, the dose may be delivered at a constant current to preventnerves in the region of treatment from being stimulated and causingmuscle contraction. The magnitude of current delivered may be adjustedduring treatment to allow pain and treatment time to be minimized. Careshould be taken however, because a fast rate of current change may causepatient discomfort and muscle twitch. Thus, in some embodiments, it maybe advisable that any change in the current delivered be done at a rateno greater than 10 mA/s to prevent muscle contraction and patientdiscomfort. A suitable rate of change is approximately 1 mA/s.

FIG. 14 illustrates current 90 increased gradually when current deliveryis started to prevent the stimulation of nerves. Current 90 is alsodecreased gradually when current delivery is terminated. The increase ordecrease may occur in steps of amplitude and period with the ramp rateequal to the step amplitude divided by the step period. The upper limiton the amplitude for preventing nerve stimulation is 0.5 mA forincreasing current. A suitable embodiment is approximately 0.2 mA forincreasing the current. The upper limit on the amplitude for preventingnerve stimulation is 1 mA for decreasing current. A suitable embodimentis approximately 0.5 mA for decreasing the current. Regardless of theslowness of the period of the steps, a large enough amplitude step willcause nerve stimulation. For amplitudes below that limit, there is aminimum limit on the period for preventing nerve stimulation. Smallamplitude steps can still cause nerve stimulation if the steps occur tooquickly and result in a ramp rate greater than 10 mA/s. The ramp rate(slope of broken line 92) should ideally be as great as possible withoutresulting in a high risk of nerve stimulation. If the step amplitudesare low enough, capacitance in the circuit may cause the output to lookless like steps and more like a straight line (such as broken line 92),which may help to reduce the risk of nerve stimulation. Theseobservations also apply to ramping down the current.

In some embodiments, an independent current source may be used todeliver the current for each electrode pair in order to control thecharge passing through each electrode and thus the size of the treatmentzone. Changing impedances at individual electrodes throughout thetherapy session may lead to an unpredictable imbalance in treatmentzones if multiple cathodes and anodes are put on a single currentsource. If multiple electrode pairs are placed on a single currentsource, the treatment zones may be controlled by putting a coulombcounter on each electrode and directing the desired amount of charge toeach electrode.

The acidic and basic zones are created by the following chemicalreaction:

H₂O−e ⁻→½O₂+2H⁺(Acid)  Anode Reactions:

2H₂O+2e ⁻→H₂+20H⁻(Base)  Cathode Reaction:

The anode reactions also include a chlorine reaction that producesmolecular chlorine. The molecular chlorine reacts with water to formhypochlorous acid, chloride and hydrogen ions. These reactions occurwithin both benign and malignant tissue including prostate. A marker,such as an ultrasound marker, may be provided to indicate pH in realtime during treatment.

The anode and cathode reactions create cell necrosis within thetreatment zone. The cathode causes necrosis via a combination ofliquefaction cell necrosis and coagulation cell necrosis. The anodecauses necrosis via coagulation cell necrosis. Cell necrosis occurs innormal prostate tissue, hyperplastic prostate tissue, and malignantprostate tissue. Accordingly, dosage and configuration may be optimizedto generally limit the treatment area to the hyperplastic prostatetissue.

FIGS. 15a and 15b illustrate images of necrosis within necrotic prostatetissue caused by DC ablation at a cathode and an anode. FIG. 15aillustrates liquefaction necrosis histology at the boundary of a cathodetreatment zone. Normal tissue is shown at 131 and liquefaction necrosisis shown at 133. As shown, a transition zone exists at 135 with aliquefaction necrosis boundary 137 being formed. FIG. 15b illustratescoagulation necrosis histology at the boundary of an anode treatmentzone. Specifically, normal tissue is shown at 131 and coagulationnecrosis is shown at 139.

Liquefaction necrosis and coagulation necrosis create a change in thestructure in the prostate as the affected tissues become fibrous and areabsorbed into the body through its natural healing process. This thuscauses removal of cellular mass, leaving a void. Because the treatmentzone is predictable, the void is predictable. By removing cellular masswithin the prostate, the interior of the prostate is debulked and excesspressure placed on the prostatic urethra is reduced. This reduction inpressure on the urethra reduces or eliminates BPH symptoms, sometimesreferred to as Lower Urinary Tract Symptoms (LUTS). It is an advantageof DC ablation over other techniques that the outer wall of the prostateis more resistant to damage caused by the electrochemical reaction thanis inner prostate tissue. Hence, a set of electrodes not perforating theouter wall but close to the wall destroys the desired prostate tissueinside the boundary formed by the wall and not the wall itself. Theouter boundary generally appears to be more chemically robust as well asproviding a mechanical boundary. Thus, while thermal energy does notrespect the tissue plane, DC ablation does.

In some embodiments, the electrodes may be withdrawn, the catheterrepositioned, and the electrodes redeployed to cover the desiredtreatment zones. In other embodiments, the number of electrodes providedis sufficient to provide treatment without redeployment of the system.

Once the reactions leading to cell necrosis have begun, the electrodesmay be withdrawn and the catheter is withdrawn. In some embodiments, theelectrodes are withdrawn into the catheter and the catheter iswithdrawn. Withdrawing the electrodes into the catheter may compriserelease of a trigger or slide in the handle, may comprise collapsing theelectrodes by sliding a sheath over the electrodes, or may be done inother suitable manner. In some embodiments, the electrodes and thecatheter are withdrawn simultaneously.

The liquefaction and softening of treated tissue around the cathoderesults at least from elevated pH; elevated pH causes necrosis and celllysis. Rupture of the cell wall causes the rigid pathologic tissue tosoften, relieving symptoms of BPH related to excess compression of theurethra. This effect can be employed to advantage in the removal ofelectrodes. Changing the polarization of each electrode to cathodic atsome time during treatment will soften the area and allow easier removalof the electrode. Likewise, inserting the electrodes may be eased bymaking each one cathodic during the insertion. If tenting of the urethrais evident during insertion, causing each electrode to be cathodic atthat time can soften the urethra at the electrode tip sufficiently toallow easier penetration without significant additional damage to theurethra

For example, with some physiologies it may be difficult to penetratelumens, such as the urethra, and tissue with a fine electrode. Chemicaldrilling may be used to aid in tissue penetration. More specifically, DCablation may be used to help penetrate the tissue. In some embodiments,all of the electrodes may be negative or cathodic to aid in tissuepenetration. This takes advantage of the inherent electro-osmosis of DCablation where fluids are drawn to the cathodes and the tissue becomesedemic. The gelatinous tissue so treated is more easily penetrated.Thus, in some embodiments, the electrode may be activated when firstcontacted with the tissue but before advancement into the tissue. Theelectrodes may be advanced during pre-treatment or pre-treatment may bedone for a short period of time, for example approximately 30 seconds,and the electrodes then advanced.

FIG. 16 illustrates a view of electrode deployment into pretreatedtissue. As shown, the tissue 142 includes a pretreated region 144 thatis substantially gelatinous. The electrode 140 is able to more easilypenetrate the tissue 142 in the gelatinous region 144.

FIGS. 17a and 17b illustrate a further embodiment to facilitateelectrode penetration. In another embodiment of urethral preparation, avacuum may be used to put the urethra in direct and firm contact withthe catheter of a system for treating tissue as provided herein. Directand firm contact of the urethra with the catheter facilitates piercingof the urethra by electrodes. With some physiologies, the urethra mayhave a larger cross section than the catheter placed therein. Thisincreases column strength requirements for the catheter and makes itmore difficult for the electrodes to pierce the catheter. For example,the urethra may expand and not be penetrated by the electrodes or theelectrodes may buckle against the urethra. FIGS. 17a and 17b illustratea system for tissue treatment including a catheter 146 and electrodes149. The figures illustrate an end view with the system deployed throughthe urethra 148. FIG. 17a illustrates electrodes 149 deployed (withoutvacuum) and causing expansion of the urethra 148. As shown in FIG. 17b ,by drawing the urethra 148 firmly against the catheter 146, for exampleby vacuum force, the electrodes 149 more easily penetrate the urethra148. Thus, the electrodes 149 may be deployed relatively immediatelyafter drawing of the urethra 148 against the catheter 146. FIG. 17billustrates electrodes 149 penetrating the urethra 148, with the urethra148 vacuumed to the catheter 146.

FIG. 18 illustrates an embodiment of a system for treating tissueincluding vacuum ports at the electrode holes. As shown, the system 150includes a catheter 152 having a proximal end 154 and a distal end 156.As shown, the catheter 152 is configured to extend through the urethra158. A balloon or other fixation element 160 is provided at the distalend 156 of the catheter 152 and is shown deployed in the bladder 162. Aplurality of electrode holes 164 are provided at a distal portion, nearthe distal end 156, of the catheter 152. The electrode holes 164 operatefor facilitating deployment of electrodes 165 from the catheter 152 andalso operate as vacuum ports. A vacuum connector 166 and an electricalconnector 168 are provided at the proximal end 154 of the catheter 152.The vacuum connector 166 may couple to a syringe or other means forachieving a vacuum. Drawing a vacuum before electrode penetration mayfacilitate use of smaller electrodes. In some embodiments, the systemshown in FIG. 18 may be used for saline injection and vacuum. Morespecifically, the electrode holes/vacuum ports may be used to create avacuum and also to distribute saline. Thus, in one embodiment, vacuum isachieved during penetration of the electrodes and is followed by salineinjection for buffering during treatment.

As can be appreciated from the chemical reactions occurring at theelectrodes, gases may be generated by DC ablation. More specifically,during DC ablation of soft tissue, ions are created at the anode andcathode electrodes when current passes through the electrodes. In orderfor the current to pass, the impedance generally is stable and less thanabout 5 kΩ to prevent operating at high voltages. DC ablation createshydrogen and oxygen gas during the hydrolysis process. These gases cancause the impedance from the electrode to the tissue to spike greaterthan about 5 kΩ. This happens when the gas is allowed to build up aroundthe electrode without either diffusing into the tissue, being ventedaway from the treatment area, or going into solution in fluid around thetreatment zone. Typical impedance ranges within the prostate are betweenapproximately 300 and 500 ohms when treating with a current of greaterthan approximately 5 mA.

The amount of current delivered affects the amount of gas created. Therate at which gas is created is directly proportional to the current atwhich it is delivered. For soft tissue applications such as theprostate, DC ablation generally may be delivered between approximately10 mA and approximately 50 mA. Generally, at currents higher than 50 mA,gas created by the treatment may not have sufficient time to dissolve,diffuse, or vent. 75 to 100 mA may be used to decrease treatment time ifgas is able to sufficiently vent. Conversely, at currents lower than 10mA, the body's buffering may reduce effectiveness of the treatment. Inone embodiment, current level is between approximately 25 mA and 40 mA.

Generally, the amount of gas generated by treatment is determined bydosing. The amount of gas generated typically increases as currentincreases. In various embodiments, the system may be provided withmechanisms for venting the gases generated. Means for venting the gasesmay be provided within the electrodes, within the catheter, or other.Accordingly, the method for BPH treatment may further comprise ventinggases created during treatment. Removal of the gases may lower theimpedance and impedance fluctuations seen by the electrodes, therebypermitting continued treatment in the desired range of current andvoltage. A first embodiment of a mechanism for venting gases is shown inFIGS. 19a -19 c.

FIGS. 19a-19c illustrate relevant anatomy to BPH treatment including thebladder 303, urethra 304, and prostate 305. FIGS. 19a-19c furtherillustrate a catheter 300, balloon 301, electrodes 302, and gaps 307. Asshown in FIG. 19a , the balloon 301 is located in the bladder 303 andinflated. The electrodes 302, having punctured the urethra 304, residewithin prostate 305 either prior to or after applying current for DCablation. In FIG. 19b , the catheter 300 has been pushed forward withforce 306 towards the bladder 303 prior to applying current but afterdeploying electrodes 302. Force 306 holds the electrodes 302 in theposition shown in FIG. 19b . This creates gaps 307 in the prostate 305between the original electrode position of FIG. 19a and the new positionof FIG. 19b . The gaps 307 serve to provide a path for the gasesgenerated during DC ablation to escape. In an alternative embodiment,shown in FIG. 19c , the catheter 300 may be pulled away from the bladder303 after deploying the electrodes 302.

A second embodiment of a mechanism for venting gas is shown in FIGS. 20aand 20b . In yet another embodiment, the electrodes 302 may be rotatedfollowing deployment, as shown in FIGS. 20a and 20b . In FIG. 20a ,electrodes 302 are shown deployed in prostate 305. The broken linerepresents the balloon 301. In FIG. 20b , the catheter 300 has beenrotated by force 306, causing the electrodes 302 to assume a newposition and opening up gaps 307 through which the gases may escape. Inalternative embodiments, other means for removing gases may be used. Forexample, gas may be vented by having a negative pressure in the deliverysystem or catheter to effectively vacuum gas away from the activeelectrode(s).

FIGS. 21a and 21b illustrate an embodiment comprising of two axialplanes of four electrodes and illustrate the axial electrode spacing andangular separation. FIG. 21a is a coronal or top view and FIG. 21b is atransverse or end view. The system is shown including a catheter 200, aplurality of electrodes including two electrodes 202 on one side of thecatheter 200 and two electrodes 204 on the other side of the catheter200, and a fixation element 205. The catheter 200 is deployedtransurethrally and the fixation element 205 positioned in the bladder206 such that deployment of the electrodes 202 is into the prostate 208.As shown in FIG. 21a , an axial spacing 210, comprising the distancebetween the electrodes 202 or 204 on each side of the catheter 200, isprovided between the electrodes 202 or 204. Dashed lines 209 indicatethe longitudinal position of the electrodes 202 relative to the catheter200. As shown in FIG. 21b , an angular spacing 212, comprising thedistance between the electrodes 202 or 204 on each side of the catheter200, is provided between the electrodes 202 or 204. The angular spacingis the angle between the posterior and anterior electrode on each sideof the catheter. Providing multiple electrodes to an area to be ablatedcan reduce the number of coulombs or the dose required from eachelectrode, thus decreasing the amount of gas created at each electrode.In some embodiments, no single electrode delivers more thanapproximately 72 coulombs. In one embodiment, each electrode deliversbetween approximately 24 and 48 coulombs of charge with an axialelectrode spacing (measured down the catheter) of approximately 8 to 10mm and an angular separation of between approximately 15 to 65 degrees.A suitable angular spacing is approximately 30 to 45 degrees with 35degrees being optimal in certain embodiments. The axial spacing could beincreased to 12 to 16 mm and up 20 mm if the dosing is increased. Theaxial separation could be reduced to 4 to 6 mm if dose per electrode isreduced and the number of electrodes is increased.

During treatment, the electrodes may lose ohmic contact with differenttypes of tissues, thereby making it difficult to deliver the desiredcurrent. When contact is lost, it can cause the treatment zone to becomemore unpredictable and muscle contractions can occur due to spikes involtage and current. Loss of contact may take place for multiple reasonsincluding, at least:

1) Hydrogen gas created from the cathode reaction or oxygen gas from theanode reaction may saturate the electrode surface and cause an increaseof impedance;

2) Chlorine gas created from the anode reaction may saturate electrodesurface and cause an increase of impedance; and

3) The reaction at the anode may cause local dehydration and cause thetissue proximate to the electrode to lose its conductive properties.

In some embodiments, actions may be taken to prevent an increase inimpedance or to counteract an increase in impedance arising at leastfrom these sources. In one embodiment, a positive force may be added tothe tissue using the active portion of the electrode, by the shape ofthe electrode design, or by using an array of electrodes and sequencingthe therapy to allow natural diffusion within prostatic tissue toovercome the increase of impedance at the electrode site. Force to theelectrode can be accomplished by adding a torque, an axial load down theelectrode, or an axial load down the catheter.

In another embodiment, an array of electrodes may be used includingeither or both of multiple cathodes and anodes in parallel with eachother to deliver the therapy. For example, as shown in FIGS. 22a and 22c, multiple anodes and multiple cathodes may be provided in parallel.FIG. 22a illustrates a first anode 222, a second anode 220, a firstcathode 226, and a second cathode 224. FIG. 22a further illustrates thetreatment areas 223 and 227 associated with the anodes 222, 220 and thecathodes 226, 224, respectively. Generally, each electrode of an anodepair or cathode pair may be at approximately the same potential and beplaced in close proximity. Providing electrodes in parallel and in closeproximity can ensure continued treatment even if one electrode losescontact. More specifically, if one anode (or cathode) of an anode (orcathode) pair loses contact, the area will continue to be treated by theother anode (or cathode) in parallel. This is true whether the electrodepair is an anode pair or a cathode pair. FIG. 22a illustrates a pair ofanodes 220 and 222 in parallel and a pair of cathodes 224 and 226 inparallel. FIG. 22b illustrates an electric current diagram for FIG. 22a. FIG. 22c illustrates the effective treatment areas 230 and 228resulting from R1 and R2, respectively, of FIG. 22b . As shown, theeffective treatment areas 230 and 228, or areas ablated, approximatesthe effective treatment areas 223 and 227 of FIG. 22a , where noimpedance problems occur. While FIGS. 22a-22c illustrate two anodes andtwo cathodes, more than two electrodes may be put in parallel.

In one embodiment, the generator may be configured to monitor ameasurement of impedance between the electrodes and uses a pattern ofimpedance measurements to predict a significant increase in impedance.Upon prediction of an increase in impedance, the generator reduces thecurrent level or turns off the current, thereby preventing a currentspike that could cause nerve stimulation.

Various current delivery mechanisms may be used to reduce the likelihoodof stimulating nerves. In one embodiment, the generator utilizes acurrent source circuit with a high voltage compliance. Voltagecompliance (or compliance voltage) is the maximum voltage a currentsource will go to in its attempt to source the programmed current.Compliance voltage values may be user settable, allowing user controlover the sourcing and measurement process. If the generator voltagecompliance is higher than the current level multiplied by the impedance,the current is controlled and current spikes are substantiallyprevented. For example, a voltage compliance of 200 V allows the currentsource to deliver a current of 20 mA without current spike due to animpedance change of 10 kΩ.

The likelihood of sudden impedance changes can be reduced by using lowcurrent, such as less than or equal to about 30 mA. The low currentsubstantially prevents the gas generation rate from greatly exceedingthe rate that the gas escapes from and/or diffuses into tissue.

In another embodiment, to reduce the likelihood of sudden impedancechanges and to complete treatment in a relatively short time frame,treatment may be started with a relatively high current, for exampleapproximately 50 mA, and the current level may be reduced one or moretimes during the treatment, for example to a level less than about 20mA. At the start of treatment, using the high current level, gas isgenerated at a high rate. Before enough gas accumulates to cause theelectrode to lose contact with the tissue, the gas generation rate isdecreased, by reducing current level, to better balance the gasgeneration and gas escape/diffusion rates.

In yet another embodiment, a low level current (between approximately 1mA and approximately 2 mA) can be applied for a short time (for example,less than about 5 minutes) before ramping up the current level. With theshort delivery of a low level current, the area around the anodedehydrates and holds the anode in place. The forced contact betweenelectrode and tissue may reduce impedance levels.

In a further embodiment, a low level current (between approximately 1 mAand approximately 2 mA) of opposite polarity from what will be used inthe treatment may be applied for a short time (for example, less thanabout 5 minutes) before ramping up. The current may change theproperties of the tissue around each electrode to reduce an impedanceproblem before ramping up the current.

System for Treatment

Returning now to FIG. 2a , FIG. 2a illustrates an embodiment of a system10 for treating tissue with a delivery system or catheter to createnecrosis within soft tissue. The system includes a delivery system orcatheter 14, which may include a mechanism for deploying electrodes 18,a generator 12, and an electrical connection 16 between the generator 12and the catheter 14. The system 10 makes electrical connections(isolated from fluids) to the power generator 12, thereby energizing theelectrodes 18. The embodiment in system 10 further facilitateslongitudinal retraction of the electrodes 18 into the catheter 14 foratraumatic introduction and removal.

FIGS. 23a and 23b illustrate example embodiments of a catheter 300 foruse with the system 10. FIG. 23a is an exploded view of a catheter body300 comprising an outer body and an inner body. The catheter outer bodyincludes a tip 301, an electrode director 302, a sleeve 303, a firstradiopaque marker 304, a second radiopaque marker 305, and routing holes308. The catheter inner body includes an actuator 306, connectionchannels 307, and a plurality of electrodes. As assembled, the systemmay be (other than at its proximal end) approximately 20 french orsmaller. Each of the portions of the catheter body 300 may bemanufactured from a different material or may be manufactured from thesame material. FIG. 23b illustrates an assembled catheter body 300 witha deployed electrode 309.

The tip 301 is provided at a distal end of the outer portion of thecatheter body 300. In the embodiment shown, the tip 301 is angled andprovides atraumatic introduction and removal. In one embodiment, the tip301 may be manufactured of a compliant material such as silicone,urethane, or PEEK. A plurality of straight electrodes are providedwithin the outer sleeve. The number of electrodes may vary fromapproximately 2 to approximately 12. Most physiologies may be treatedwith 4 to 8 electrodes. The plurality of straight electrodes are routedto and from the tissue through the electrode director 302. Theelectrodes may be semi-rigid: sufficiently flexible to extend throughrouting holes 308 in the outer sleeve 303 but sufficiently rigid topenetrate tissue. The electrodes may be corrosion resistant, such as byproviding a corrosion-resistant layer over the electrodes. The electrodemay comprise a nitinol wire with a corrosion resistant layer such asplatinum or another noble metal.

The actuator 306 and associated electrodes may be provided within theinner portion of the catheter body 300. As may be appreciated by oneskilled in the art, actuation may be linear or rotational and is basedupon coupling of the electrodes to a portion of the catheter body and/ora handle. The electrodes may be coupled to the actuator 306 and may becorrosion resistant and sufficiently flexible to extend through therouting holes 308 and sufficiently rigid to penetrate tissue. Theactuator 306 may be configured to move linearly along the length of thecatheter. As previously discussed, the catheter body may include aninner body and an outer body; these may variously be referred to as theinner and outer body, the inner and outer sheaths, or the inner andouter sleeves. The inner body may include a plurality of crimped tubesfor receiving the electrodes. These tubes are referred to as connectionchannels 307 and permit multiple straight electrodes to deploy withmaximum column strength and to connect to flexible conductors in theinner body of the catheter. The electrodes are anchored in the innerbody parallel to overlapping sleeves. Deployment of the electrodes maybe affected via actuation of the inner actuator 306 in a distaldirection with respect to the outer sleeve 303. The outer sleeve 303directs the electrodes outwardly for treatment.

The electrode director 302 may have distal and proximal radiopaque orhyperechoic markings 304 and 305 to facilitate placement of theelectrodes in a desired location. The markings 304 and 305 may beinsulated to protect against exposure to the pH formed from the anodeand cathode reactions, providing greater biostability. Such insulationmay be provided by an outer sleeve of the catheter tip 301 and sleeve303.

One or more anchoring features, described more fully with respect toother embodiments, may be provided to fix the system atraumatically inplace for treatment. Generally, the anchoring features may comprisecomponents that expand diametrically and lock in place when shortened toanchor the system within the urethra. Anchoring may provide linearand/or rotational stability to the system. First and second anchoringfeatures may be provided, with the first being positioned distal of thetreatment zone and the second being positioned proximal of the treatmentzone.

FIGS. 24a and 24b schematically illustrate a system 310 for non-thermalDC ablation placed for soft tissue ablation with a trans-lumen catheter(e.g. urethral, esophageal, vascular, rectal, tracheal). The system 310includes elongated airless anchors 312 and electrodes 314.

FIG. 24a illustrates the system 310 with the elongated airless anchors312 in a collapsed condition. FIG. 24b illustrates the system 310 withthe elongated airless anchors 312 in an expanded condition. Generally,an airless anchor may be an anchor that can be mechanically manipulatedfrom a collapsed condition to an expanded condition. For example, anairless anchor may comprise a metal mesh structure that is extended tocollapse and then pressed together to expand outwardly. The inneractuator and outer sleeve may be coupled to a proximal end of the leadto facilitate user extension of the electrodes and expansion of the leadanchors. Another embodiment for an anchoring system is using inflatableballoons with saline or air. In one embodiment, the system includes oneinflatable balloon which anchors the catheter in the bladder.

FIG. 25 illustrates a system for soft tissue treatment configured forinsertion through a body lumen until the distal end of the device is inproximity to the tissue to be treated. In the embodiment shown, a distalballoon is inflated and the device is retracted into treatment position.Further, a proximal balloon may be inflated to hold the device inposition and prevent the device from rotating while the electrodes aredeployed. The ends of the electrodes may be uninsulated, may comprise amaterial resistant to electrochemical corrosion, and may have adjustablepositions relative to the catheter, thus controlling the position andsize of the treatment zone. When the treatment is completed, theelectrodes are retracted, and the device removed.

The system may be positioned using the distal balloon 405 deployed fromthe distal tip 401 of the catheter. In one embodiment, the distalballoon is silicone and has a low inflation pressure. When deflated, thedistal balloon 405 may have substantially the same shape as the tip 401of the catheter and may be fit tightly to the tip 401. An air pressurepathway for inflation of the distal balloon 405 may be provided throughthe center of the tip. While each of the balloons discussed herein isdiscussed with respect to air inflation of the balloon, it is to beappreciated that the balloon may alternatively be inflated using anyfluid. For example, in an alternative embodiment a saline solution maybe used to inflate the balloon. The balloon could be inflated withbetween 5 and 60 cc of fluid or air to ensure adequate anchoring in thebody's lumen. A suitable volume of fluid is 5 to 15 cc of saline.

FIG. 25 illustrates the catheter 400 with the proximal and distalballoons 404 and 405 inflated and the electrodes 406 in an expandedconfiguration. The distal balloon 405 is located proximate to the tip401 and is coupled to the outer sheath of the catheter. An electricalwire attaches to each row of electrodes and runs through the innersheath of the catheter 400 to wire/air pressure tubing in the handle.The uninflated proximal balloon 404 is attached to the outer sheath ofthe catheter 400.

The proximal balloon 404 is coupled to the outer sheath 413 of thecatheter. In one embodiment, the proximal balloon 404 may have arelatively long length to minimize patient discomfort associated withballoon inflation. For example, the proximal balloon 404 may beapproximately 5 cm long. Like the distal balloon 405, the proximalballoon 404 may comprise silicone and have a low inflation pressure.

As shown in FIG. 25 the distal balloon 405 inflates and locates thedevice near the tissue to be treated. The proximal balloon 404 inflatesto approximately the size of the lumen to hold the linear and rotationalposition of the device in the lumen. The electrodes 406 extend throughpositioning holes 407 in an electrode director that directs theelectrodes at a desired angle. As previously discussed, the electrodesmay have axial electrode spacing and angular separation. The electrodesmay be axially spaced, for example, 1 centimeter apart with one rowangled up to both sides at a 15° angle to the horizon (assumingpositioning line is up). Further, one row of electrodes may be angleddown at 40° on both sides. In one embodiment, the anterior electrodesmay be 8 mm apart with the electrodes at 0 degree angle to the horizonand the posterior row angled down at 35 degrees into the tissue.

In accordance with various embodiments provided herein, the deliverycatheter may deploy between 2 and 12 electrodes into the soft tissueadjacent to the lumen in which the catheter resides. The number ofelectrodes used may depend on patient physiology. In some embodiments,the system may be configured with two or four electrodes exiting thecatheter in parallel in a plane approximately created by points an equaldistance from the proximal edge of the balloon. In other embodiments theelectrodes may not exit the catheter in parallel or from the same planewithin the catheter.

FIGS. 26a and 26b illustrate a system having a forward angling electrodearray. As shown, the system 501 includes a catheter 503, electrodes 500having a length of extension 505, and a fixation element 504. Theelectrodes 500 may be introduced into the soft tissue 502 anglingtowards the balloon at an angle 507 between 15 and 60 degrees. This typeof electrode array will be called a forward angling electrode array.FIG. 26b illustrates angling of a posterior electrode 500 a and ananterior electrode 500 b. Other embodiments include a lateral electrodearray having electrodes which extend out at an angle from 60 degrees to120 degrees from the balloon along the catheter body, and an invertedelectrode array which has an angle between 120 degrees and 165 degrees.In one embodiment, a forward angling electrode array has a 45 degreeangle towards the distal end of the catheter.

The electrodes 500 may be introduced through the lumen 10 to 20 mm fromthe proximal edge of the fixation element 504. In one embodiment, anapproximately 30 degree forward angle electrode may exit the catheterapproximately 16 mm from the fixation element. In another embodiment, anapproximately 45 degree forward angle electrode may exit the catheterapproximately 14 mm from the fixation element. In yet anotherembodiment, an approximately 15 degree forward angle electrode may exitthe catheter approximately 18 mm from the fixation element. It isappreciated that small changes in this dimension will have only smallchanges on the safety and efficacy of treatment. Mismatch of forwardangle and the distance between electrode and the fixation element mayhave undesirable effects on safety and efficacy.

In some embodiments, the electrodes 500 may extend from the catheter alength of extension 505 of approximately 14 to 22 mm. In one embodiment,the length of extension may be approximately 18 to 20 mm for a forwardangling electrode array.

Referring to FIG. 26b , the anterior electrodes 500 b may be configuredto protrude from the catheter 503 at an angle between −15 and 15 degreesfrom the horizontal axis. In one embodiment, the anterior electrodes 500b may be configured to protrude from the catheter 503 at anapproximately 0 degree angle from the horizontal axis. This includesforward, lateral and inverted electrode arrays.

The posterior electrodes 500 a may be configured to protrude between 25and 65 degrees from the anterior electrodes 500 b. In one embodiment,the posterior electrodes 500 a protrude approximately 35 degrees fromthe anterior electrodes 500 b. This includes forward, lateral, andinverted electrode arrays.

In various embodiments, the active portions of the electrode may bebetween approximately 4 and 12 mm long at the end of the insertionlength of the electrodes as they deploy into the prostate tissue. In oneembodiment, the active portion of the electrode may be betweenapproximately 6 and 8 mm. This allows for between 10 to 14 mm ofinsulation on the electrodes in the preferred embodiment for lumenprotection in a forward angling electrode array.

FIG. 27 illustrates an 8-electrode array in two rows of four electrodes(posterior electrodes are not shown as they are aligned with theanterior electrodes). This catheter is optimized for prostate treatment,however may also be used to treat tissues adjacent to other lumens inthe body. As shown, the system 501 includes a catheter 503, electrodes500 and 500 c, and a fixation element 504. The electrodes 500 may beintroduced into the prostate 502 angling towards the balloon at an anglebetween 15 and 60 degrees. Generally, an 8-electrode array may beconfigured similarly to the 4-electrode array shown in FIGS. 26a and 26bwith the addition of a proximal plane of 4 electrodes 500 c which arespaced approximately 6 to 12 mm from the distal 4 electrodes 500. In oneembodiment, the spacing between the first array of electrodes 500 andthe second array of electrodes 500 c may be approximately 8 mm.

In another embodiment the electrodes may be staggered such that they donot align. In another embodiment 3, 5, 6, 7, 9, 10, 11, and 12 electrodearrays may be utilized to treat soft tissue with DC ablation through alumen and into the tissue adjacent to the lumen.

Each of the embodiments of the system for treating tissue comprisescatheters and electrodes as described above and further comprises anelectronic control system or generator. The electronic control system orgenerator may be connected to the catheter by an extension therapy cableto transfer the DC current controlled by the generator into the catheterthat is delivered through the tissue contacting electrodes. In someembodiments, the extension therapy cable may be between approximately 3and 20 ft in length. In one embodiment, the therapy cable isapproximately 10 ft in length.

FIG. 28 is a block diagram of a generator 600 in accordance with oneembodiment. A main microcontroller 601 communicates with a currentsource microcontroller 602, 603, 604 contained in each isolated currentsource 605, 606, 607 respectively. The main microcontroller 601 alsocontrols the operator interface. Although FIG. 28 shows three isolatedcurrent sources, this is intended to be illustrative only and any numberof current sources may be used. To control the timing of the therapy,the main microcontroller 601 may utilize, for example, a clock 608powered by battery 609. As is standard in the art, the microcontrollermay utilize a memory 610 and switches 611 and may utilize a display 612,as well as an alarm 613 and an isolated serial interface 614. Anisolated power supply 615 may be provided to power the mainmicrocontroller 601 and the isolated current sources 605, 606, 607.Using isolated current source 605 as an example, each current source mayinclude a current source microcontroller 602, a D/A converter 616, anisolated DC converter 617, an electrode interface 618, and an isolationcircuit 619.

The current or voltage level and amount of charge to be delivered by thegenerator 600 may be programmable and may be set via switches 611 anddisplay 612. The generator 600 can function as a stand-alone device ormay be controlled by an external controller such as a personal computerin which case treatment parameters may be set via the personal computer.The generator 600 may automatically set current, voltage and charge forall current sources based upon a setting entered by the user. The sizeof the treatment zone is dependent on the amount of charge delivered tothe electrodes as well as the electrode shape and size. The treatmenttime is dependent on the current level and the amount of chargedelivered. Different current sources 605, 606, 607 may be programmedwith different settings to make treatment zone shapes and sizes matchprostate (or other tissue) anatomy.

The generator 600 may contain any suitable number of individual currentsources 605, 606, 607. When more than one current source is used, eachcurrent source may be isolated from the other current sources. Isolationbetween current sources may be used to improve control of currentdelivery. Without isolation between current sources, current may flow inthe lowest impedance path which could cause some electrodes to delivermore treatment than intended and others to deliver less treatment thanintended. Patient safety isolation may be provided by isolated powersupply 615 and isolated DC converter 617 as well as isolation 619. Eachof the independent current sources can be programmed to deliver adifferent dose and can be also programmed as anode or cathode. Mainmicrocontroller 601 software permits only logical selections of anodesand cathodes.

The generator 600 may further measure the current delivered and thevoltage between anodes and cathodes. It can stop current delivery whenthe correct charge has been delivered. It can also cease currentdelivery if it detects current or impedance faults.

In one embodiment, the generator may be designed to deliver current tomultiple electrodes simultaneously and to control the amount of currentdose to each electrode. In some embodiments one generator may be used tocontrol between one and 6 pairs of electrodes. In one embodiment, thegenerator may be designed to control four pairs of electrodes. A systemfor treating tissue using DC ablation, as provided herein, may use acontrolled dosage of current delivered to more than two electrodes. Whenthe impedance between each electrode and its surrounding tissue isdifferent, the current flows through the lowest impedance path, whichmay result in some electrodes delivering more current than others. Thus,the generator may be designed to control the current to each electrode.

Systems and methods for current source isolation are thus provided.Current to each electrode may be controlled by electrically isolatingeach current source from all of the other current sources. Toelectrically isolate a current source, its power source may be isolatedfrom the power sources of other current sources. Thus, in oneembodiment, shown in FIG. 29a , a separate battery 630 and DC/DCconverter circuit 631 is provided to power each current source 632, withthe batteries 630 electrically isolated from each other. In anotherembodiment, shown in FIG. 29b , a single power source 634 is used forall current sources 632 and a transformer based isolation circuit 636 isprovided for each current source.

Systems and methods for signal isolation are further provided. Toelectrically isolate each current source, the signals that control thecurrent level and provide measurements may be isolated from othercurrent sources. Such isolation may involve optical isolation, isolationamplifiers, differential amplifiers, and transformer isolation. Withoptical isolation, digital signals may be transferred between isolatedand non-isolated circuits using the optical isolation components. Analogsignals can be converted to digital signals using an A/D converter andthen can be transferred between isolated and non-isolated circuits usingthe optical isolation components. With isolation amplifiers, analogsignals can be transferred between isolated and non-isolated circuits.With differential amplifiers, analog and digital signals can betransferred between isolated and non-isolated circuits. The differentialamplifier circuits may utilize large resistor values to provideisolation. With transformer isolation, digital signals can betransferred between isolated and non-isolated circuits usingtransformer-based circuits. Analog signals can be converted to digitalsignals using an A/D converter and then can be transferred betweenisolated and non-isolated circuits using transformer-based circuits.

Current to each electrode can be controlled using a separate circuit forcontrol of the current to each electrode. Further, the amount of currentdelivered to each electrode can be controlled by measuring the currentand charge delivered to each electrode and changing the current sourcesettings to control current delivery. The generator thus may be providedwith the ability to control the polarity of each electrode and tocontrol whether each electrode is connected to the current source.

FIG. 30 shows a generator embodiment with electrode control circuits.The generator can switch the electrode pairings and polarities tocontrol which electrodes are delivering current. As shown, a currentsource 650 delivers current to four electrodes 652, 654, 656, and 658.Switches 660 are provided through which the generator can delivercurrent to any of the electrodes (independently) and can control whethereach electrode 652, 654, 656, 658 acts as an anode 662 or a cathode 664.The generator can further measure the current in each electrode 652,654, 656, 658 and turn off certain electrodes or change the electrodepairings to control which electrodes deliver current. When an electrodehas delivered the charge it was supposed to deliver, it can be turnedoff. The total current level (mA) can be adjusted.

In accordance with a further embodiment, the generator may be configuredto detect current delivery faults, notify users of detected faults, andadjust current delivery to assure patient safety. A variety of faultsmay occur during any treatment involving stimulation via electrode,including DC ablation treatment. These faults include, for example,contact between electrodes causing a short circuit and reducingeffectiveness of treatment, high impedance between an electrode andtissue causing little current to be delivered and resulting in little orno treatment, and interaction between electrodes causing some electrodesto deliver more current than expected and other electrodes to deliverless current than expected. In some embodiments, the generator may beconfigured to detect these faults and notify the user and/or stoptreatment to assure patient safety.

In an embodiment for impedance fault detection, the generator canmeasure the voltage between electrodes and the current being delivered.These measurements may be used to calculate an inter-electrodeimpedance, which is equal to the voltage divided by the current. If avery low impedance (short circuit) or a very high impedance (opencircuit) is detected, the generator can notify the user. For example,the generator may show a message on a display of the generator, maysound an alarm, or other. In further embodiments, the generator can stopcurrent delivery upon detection of an impedance fault.

In an embodiment for current fault detection, the generator can measureboth the anode current and the cathode current and can compare the twomeasurements to verify that they are approximately equal or that thecurrents do not vary significantly from one another (for example,exceeding a 10% difference). If the anode and cathode currents are notequal or vary significantly, the generator can notify the user. Thedifference level required for an alarm may be set by the user.Notification may comprise showing a message on a display, sounding analarm, or other. In further embodiments, the generator can stop currentdelivery upon detection of a current fault.

When the generator detects a fault, the current source may be rampeddown to deliver no current and the generator may enter a paused state.Impedance faults may be caused by accumulation of gas around anelectrode during treatment and the condition that caused the fault mayresolve after a period of time. The generator may automatically attemptto resume, or retry, treatment after a period of time, for example from1 second to 5 minutes. If no fault is detected during a retry attempt,the current is ramped up and treatment is continued. If a fault isdetected during a retry attempt, the generator may retry again after aperiod of time. The generator may limit the number of retry attempts,for example to a number from 1 to 10. The time between retry attemptsand the maximum number of retry attempts may be factory settings. Thegenerator may also provide a button for a manual retry attempt.

Pain experienced by patients during treatment of tissue by DC ablation,as provided herein, may vary by patient. A patient may experience painduring DC ablation due to the level of current delivered via theelectrodes. For some patients, the current delivery may be painful abovea certain current threshold and that threshold may vary betweenpatients. Pain may be relative to the current delivered by one pair ofelectrodes or may be relative to the cumulative current delivered bymultiple pairs of electrodes. The DC ablation treatment time is directlyaffected by the current level. Treatment time can be reduced byincreasing current. Thus, if the patient is not experiencing pain, thecurrent level may be increased to reduce treatment time. One embodimentprovides a current generator that facilitates adjustment of currentlevel to reduce treatment time (thus increasing current) or to reducepain during treatment (thus decreasing current).

Pain associated with DC ablation may be reduced for patients who areless tolerant of the process by reducing the ramp rate of the currentand reducing the steady state current magnitude. Different patients havedifferent tolerance levels for pain and, thus, the ramp rate and currentmagnitude at steady state may vary between patients. Generally, for mostpatients, a suitable ramp rate is between approximately 0.1 andapproximately 10 mA/second. Maintaining a current level for a period oftime can reduce patient pain at any level of DC current. Thus, in oneembodiment, current levels are maintained for a period betweenapproximately 15 seconds and approximately 30 seconds.

FIG. 31 illustrates a current profile 670 for reducing pain associatedwith DC ablation. As shown, the treatment ramps to three differentlevels 672, 674, 676 of current and maintains those levels of currentfor a period of time before ramping up again. Specifically, in theembodiment shown, the current is ramped up at approximately 1milliAmpere/second. After approximately 10 seconds of ramping, thecurrent is maintained at approximately 10 mA (shown at 672) forapproximately 50 seconds (thus until a total treatment time ofapproximately 1 minute). The current is then ramped up for approximately10 seconds until a current level of approximately 20 mA (shown at 674)is reached. That current is maintained for approximately 50 seconds. Thecurrent is then ramped up again for approximately 10 seconds until acurrent level of approximately 30 mA (shown at 676) is reached. Thecurrent is then maintained at approximately 30 mA. Thus, in theembodiment shown, current is ramped up for approximately 10 seconds andmaintained for approximately 50 seconds with this being repeated until adesired current level is reached. The ramp rate (1 milliAmpere/second inthe embodiment shown) may vary as suitable for the patient and theapplication. In some embodiments, the ramp rate may vary between, forexample, 0.1 milliAmpere/second and 10 milliAmpere/second. The durationof ramping between current level maintenance and the duration of thecurrent level maintenance may also vary. While the embodiment of FIG. 30illustrates maintaining current at three levels 672, 674, 676 (10 mA, 20mA, and 30 mA), more or fewer levels of stable current may be used andthe magnitudes of current may vary, though, generally, treatment may bedone between about 10 mA and about 50 mA. Slowly ramping up the currentrate and maintaining the current at interim levels can reduce the amountof pain experienced by a patient who is more sensitive to pain—forexample, one who has received suboptimal anesthesia.

In yet a further embodiment, a resistor-capacitor (RC) and/or aninductor-capacitor (LC) filter circuit may be incorporated into thegenerator circuitry to reduce the electrical noise caused by a switchingpower supply which may reduce pain experienced by a patient.

Another technique for reducing pain associated with DC ablation oftissue as provided herein comprises adding Transcutaneous ElectricalNerve Stimulation (TENS)-like pulses to the DC voltage. FIG. 32illustrates TENS-like pulses 680 over a DC voltage 682. TENS-like pulsesadded to the DC voltage to stimulate the nervous system reduces painsensitivity in the region being treated. Pulses may be delivered at fromapproximately 10 Hz to approximately 10 kHz and can have voltages ofbetween approximately 10 mV and approximately 20V. Pulse widths mayrange from approximately 10 μs to approximately 100 ms. In accordancewith various embodiments, parameters may be adjusted depending on thetissue type being treated, the depth of treatment, and the treatmentstrength. In alternative embodiments, remote electrodes may be used. Insome embodiments, the current may be interrupted periodically for TENSstimulation. For example, the current may be interrupted every 100 μs orevery 1-10 ms for TENS stimulation.

Thus, in accordance with some embodiments, a current generator comprisesa switch, button, or other mechanism to change current levels. Thecurrent generator may recalculate estimated treatment time based on thechanged current level. The current generator may further comprise adisplay for showing the current change and/or for showing the newestimated treatment time. Accordingly, a switch may be provided that,when actuated during treatment, changes the current level by a presetamount. The switch may change the current level upwardly by the presetamount or may change the current level downwardly by the preset amount.In one embodiment, separate switches may be provided for upward currentchange and for downward current change. In an alternative embodiment, asingle switch may be provided that can be actuated in one manner tochange current upwardly and can be actuated in another manner to changecurrent downwardly. For example, the switch may have three positions, amiddle position that is neutral and does not change current, an upposition that changes current upwardly, and a down position that changescurrent downwardly. When the switch is actuated to decrease currentlevel during treatment, the current level of the current sourcedelivering the highest current is reduced by a preset amount. When theswitch is actuated to increase current level during treatment, thecurrent level of the current source delivering the lowest current isincreased by a preset amount. If the highest current level, or lowestcurrent level depending on whether the switch is increasing ordecreasing current, is delivered by more than one source, the currentlevels of all of those sources are changed. Generally, the current levelis ramped down or up, not changed abruptly, to substantially preventstimulation of nerves.

In a further embodiment, a portable generator is provided. Generally,the generator may be relatively small and have a handle. In oneembodiment, the generator has a height of less than about 100-150 mm, awidth of less than about 300 mm, and a length of less than about 400 mm.The generator includes a power connector for connecting power thereto.The connector may include electrical components for improvement ofimmunity to electromagnetic interference (EMI). The generator furtherincludes a patient cable connector for connecting a cable thereto. Thegenerator includes a computer serial port or a wireless port. Thecomputer serial port and the wireless port facilitate communicationbetween the generator and a computer or external memory device.

The generator, extension cable, and catheter each have one conductor foreach electrode and may have an additional conductor to allow thegenerator to determine whether the extension cable and/or catheter areconnected to the generator. On the catheter or extension cableconnector, the anode pin of one current source may be connected to theadditional conductor. The additional conductor may be connected to acircuit in the generator that measures the voltage of the additionalconductor. When the start button is pressed to begin therapy, thegenerator may turn on the current source connected to the additionalconductor and measure the voltage of the additional conductor. When theexpected voltage is measured, the generator determines that the catheterand/or extension cable is attached and therapy is started. When themeasured voltage is not as expected, the generator determines that thecatheter and/or extension cable is not attached and therapy is notstarted. The generator may also detect whether the extension cableand/or catheter is attached by using digital communication with acircuit in the cable or catheter, either via wires or wirelesscommunication. In one embodiment the generator may detect whether acatheter has been previously used to prevent reuse by either blowing afuse in the catheter after treatment or changing the state of atransistor in the catheter.

In accordance with various embodiments, the generator thus comprisesswitches and a display. The switches facilitate entering of settings andcontrolling of therapy. The switches may comprise membrane switches,push-button switches, may be incorporated into a display using atouch-screen format, or may have another configuration. The displayshows information to a user. The display may be, for example, a liquidcrystal display (LCD). The display may display text or may displaygraphics. The display may be monochrome or color or may be backlit. Insome embodiments, the display is a touch-screen display. Generally, theswitches may be located proximate the display to allow the user to viewthe display while actuating the switches. In touch screen embodiments,the switches may be incorporated into the display.

FIGS. 33a-33d illustrate an embodiment of a touchscreen display layoutof a generator.

FIG. 33a illustrates a Therapy Settings screen, where the dose (charge)setting for all current sources can be adjusted at the same time usingthe ‘+’ and ‘−’ buttons. Pressing the ‘Advanced Dose Mode’ button allowsfor adjusting the dose (charge) of each individual current source. Whenthe ‘Next’ button is pressed, the display goes to the screen shown inFIG. 33 b.

FIG. 33b illustrates a Therapy Ready screen. The selected dose (charge)setting is shown along with an estimated treatment time. Treatment canbe started by pressing the ‘ Start Therapy’ button. When the ‘Back’button is pressed, the display goes to the screen shown in FIG. 33 a.

FIG. 33c illustrates a Therapy Running screen. The amount of dose(charge) delivered, estimated treatment time, and elapsed time areupdated at approximately once per second while therapy is running.Pressing the ‘Source X’ button causes additional therapy information forcurrent source #X to be shown, including measurements of current andimpedance. The current magnitude may be increased or decreased bypressing the ‘+’ button or ‘−’ button. Treatment may be paused bypressing the ‘Pause Therapy’ button.

FIG. 33d illustrates an Add New Doctor screen, including a QWERTYkeyboard which may be used to enter a doctor's name. The user may cancelthe entry of the doctor's name by pressing the ‘Cancel’ button or mayaccept the name by pressing the ‘Done’ button.

FIG. 33e illustrates an embodiment of a switch and display layout of agenerator. The generator 700 includes a display 702, an increase switch704, a decrease switch 706. The switches 704, 706 may provide feedbackvia switch detent or audible beep and, in some embodiments, visualfeedback via the display. To turn the generator power on and off, thegenerator may provide separate On and Off switches 708, 710 or a singleOn/Off switch that may be actuated between positions. To start and stoptreatment, the generator 700 may provide separate Start and Stopswitches 712, 714 or a single Start/Stop switch. The generator 700 mayprovide a means for pausing treatment allowing treatment to be resumedinstead of re-started from the beginning. To pause and resume treatment,the generator 700 may provide separate Pause and Resume switches 716,718 or a single Pause/Resume switch, or a pause position on the On/Offswitch.

A mechanism for adjusting the current level while treatment is inprogress may be provided. A single switch for increasing and decreasingcurrent may be provided. In an alternative embodiment, separate switchesfor increasing current and decreasing current may be shown. In yet analternative embodiment, the generator may have a current switch, such as722 of FIG. 33e , along with up and down switches 704, 706. In such anembodiment, the setting may be changed by pressing the current switch722 followed by either the up switch 704 or the down switch 706, or bypressing either the up switch 704 or down switch 706 at the same time asthe current switch 722.

The generator further may comprise a means for entering a treatmentsetting or settings. Such mechanism may comprise switches such as thosedescribed with respect to current. Thus, a single switch may be providedfor increasing and decreasing setting. In an alternative embodiment,separate switches may be provided for increasing setting and decreasingsetting. In yet an alternative embodiment, the generator may have asetting switch, such as 720 of FIG. 33e , along with an up switch 704and a down switch 706. In such an embodiment, the setting may be changedby pressing the setting switch 720 followed by either the up switch 704or the down switch 706, or by pressing either the up switch 704 or thedown switch 706 at the same time as the setting switch 720.

In some embodiments, when entering the generator setting, the display702 may show the entered setting. If the setting is being changed, thedisplay may show the proposed new setting. Proposed new settings may beshown differently from settings that have been entered, such as byshowing proposed new settings in a blinking or flashing manner whileshowing entered settings without blinking or flashing. Accordingly, anenter switch 724 may be provided to confirm proposed settings orcurrents.

During treatment, the display 702 may show the treatment time remaining,the total expected treatment time, and the status of the generator. Thestatus may be, for example, Starting, Active, Pausing, Resuming,Changing Current Level, or Stopping. Showing the status providesfeedback to the user after a switch has been pressed.

The generator may incorporate different display modes, for example, UserMode and Clinician Mode. In Clinician Mode, the display may show moreinformation than shown in User Mode. Items that may be shown inClinician Mode may include, for example, the setting, currentmeasurement, impedance measurement, current level setting, and chargesetting.

The treatment parameters may be determined by settings entered by theuser. Generally, treatment parameters may include current level, charge,or time. Setting information may be shown on the display. Settings maybe entered by setting the parameters for each current sourceindividually or by using switches to select a current source and then toselect a parameter and a setting. Settings may be entered by setting theparameters for current sources at the same time by using switches toselect a parameter and a setting. In some embodiments, settings may beentered by selecting a setting from a settings table stored in thegenerator memory. A separate settings table may exist for each currentsource, allowing for setting up each current source individually. Asingle settings table can contain parameter settings for all currentsources, allowing for all current sources to be set up using onesetting.

In various embodiments, settings may be different for each source or allsources may be set with the same parameters. A source may be set to notturn on by setting current and charge to zero. The settings in the tablemay be programmable via a serial port included in the generator, aspreviously described. Settings in the table may have names or numbersthat correspond to a prostate size or dimension, allowing the setting tobe selected based, for example, on a prostate measurement. Settings inthe table may be provided on a label on the generator or in aninstruction manual, showing which setting to use for different prostatesizes or dimensions.

The generator may include a serial port or wireless port forcommunication with a computer. Accordingly, communication with acomputer may be via wires or may be wireless. The communicationfunctions may include programming of settings into the generator memory,remote control of all generator switch functions, the transfer ofsettings and data from the generator memory to the computer, or otherfunctions as will be known to those skilled in the art.

In some embodiments, the generator may have stored, un-alterable,settings. These settings may be referred to as Factory Settings. Thesettings may be stored in non-volatile memory to prevent them from beinglost if power is disconnected. In some embodiments, the factory settingsmay be alterable by a user under certain conditions. The FactorySettings may include:

(1) Ramp Up Rate—determines the rate that the current level increaseswhen starting or resuming treatment, 0.1-10.0 mA/second, default of 1.0mA/second;

(2) Ramp Down Rate—determines the rate that the current level decreaseswhen pausing or stopping treatment, 1-100 mA/second, default of 10mA/second;

(3) Ramp Up Step Size—determines the increment in current level duringramp up, 1-1000 microamps, default of 10 microamps;

(4) Ramp Down Step Size—determines the increment in current level duringramp down, 1-5000 microamps, default of 100 microamps;

(5) Maximum Current—sets the maximum current level that can be set foreach current source via the generator switches, 30-100 mA, default of 50mA;

(6) Maximum Charge—sets the maximum charge level that can be set foreach current source via the generator switches, 36-180 coulombs, defaultof 44 coulombs;

(7) Calibration constants—used by the generator software to improve theaccuracy of current level settings, current measurements, and voltagemeasurements, slope and intercept constants for linear fit calibration;

(8) Increase Current Step Size—determines the increment in the currentlevel setting when the Increase Current switch is pressed, 1-10 mA,default of 5 mA;

(9) Decrease Current Step Size—determines the decrement in the currentlevel setting when the Decrease Current switch is pressed, 1-10 mA,default of 5 mA;

(10) Settings table—contains the current level and charge settings foreach current source;

(11) Current level for detection of a low current fault, 75%-95% ofcurrent setting, default of 90%;

(12) Current level for detection of a high current fault, 105%-125% ofcurrent setting, default of 10%;

(13) Impedance level for detection of a low impedance fault, 10-200ohms, default of 100 ohms;

(14) Impedance level for detection of a high impedance fault, 1500-5000ohms, default of 2000 ohms;

(15) Storage Interval—determines timing for storing data to memory,1-1800 seconds, default of 60 seconds;

(16) Model number;

(17) Serial number;

(18) Date of manufacturing;

(19) Minimum number of current sources, 1-4, default of 1;

(20) Maximum number of current sources, 1-4, default of 4; and

(21) Allow user selection of number of current sources, yes/no, defaultof yes.

Accordingly, a system and method for DC ablation of tissue is provided.In some embodiments, the system and method may be used with atransurethral approach for treating cancerous tissue, xxx tissue, BPH,or other tissue by creating large lesions in less than 45 minutes. Theprocedure is minimally invasive and the patient can be fully awakeduring the procedure and only remains uncomfortable for a short periodof time. In addition, the apparatus and method makes it possible for thephysician to reduce the time required for the procedure. The apparatusand method also has an advantage in that it substantially eliminatesmultiple deployments of a device for treating tissue. This avoidsdifficulties associated with precise positioning of individualdeployments in a treating tissue. In various embodiments, the system mayoperate in a mode where not all electrodes deployed into the tissue havecharge delivered to them or have unequal charge delivered to them. It ispossible to reconfigure the electrode pairs so that large lesions can becreated without the necessity of redeployment of the device. During theprocedure, a scope may be deployed to permit viewing of either or bothpairs of needles. pH controls may be employed for monitoring andcontrolling the ablation procedure. pH sensors may be placed in variousplaces including on the catheter, on a rectal probe, or on apercutaneous needle to monitor, control, or plan the treatment.

Although the invention has been described with reference to specificembodiments, persons skilled in the art will recognize that changes maybe made in form and detail without departing from the spirit and scopeof the invention.

EXAMPLES

The following examples are for illustrative purposes only and are notintended to be limiting.

Example 1

A study was performed to evaluate the chronic effects of DC ablation incanine prostates. Eight chronic canine subjects were treated to evaluatethe healing cascade, dose response, prostate shrinkage, and the durationof time before necrotic tissues were reabsorbed into the body.

Treatment was performed on the subjects by performing a laparotomy andinserting electrodes through the prostate capsule. Treatment wasperformed at 40 mA and with a dose of between 4 and 70 C. The subjects'blood, urine, general health, and behavior patterns were monitoredbefore sacrificing them at time intervals of 1, 3, 20, 40, and 60 daysafter treatment. The prostate and surrounding tissues were dissected andexamined after sacrifice. Ultrasound and CT scans were used throughoutthe study to identify the necrotic lesions and identify any changes thattook place to the lesion.

Ultrasound, CT imaging, and visual verification during histology showedthat voids or cavities were created in the prostate tissue in thenecrotic areas induced by DC ablation. FIGS. 34a and 34b illustratesslices of prostate at 2 times of sacrifice through the center oftreatment zones. FIG. 34a illustrates a slice of prostate 20 days aftertreatment. FIG. 34b illustrates a slice of prostate 40 days aftertreatment. The necrotic tissue was substantially absorbed into the bodyby the first screening date, 20 days after treatment. Reabsorptionresulted in voids, shown in FIGS. 34a and 34 b.

The voiding within the prostates caused the overall shape and size ofthe prostate to shrink. In one subject the prostate had a measured widthof 40 mm prior to treatment. Twenty days after treatment, the prostatehad a measured width of 28 mm.

The results of Example 1 show substantially complete absorption of thenecrotic tissue with little or no fibrotic scarring. The tissue aroundthe voids created by DC ablation remains soft and pliable withoutsurrounding hardened scar tissue.

Sacrifice of the subjects and examination of the prostate showed thatthe necrotic tissue was contained within the capsule and all tissues inthe pelvic cavity remained healthy. Within the prostate itself, tissueimmediately adjacent to the necrotic zones remained healthy,illustrating a sharp diffusion gradient. The size of the voids createdcoincided with dose response algorithms previously developed. Thestudies thus confirmed that the treatment has a sharp diffusion gradientand a predictable dose response.

All subjects remained healthy throughout the study and maintained normalurination and defecation patterns without signs of straining ordiscomfort.

Histology Results: Following treatment, all animals were terminated andsubjected to necropsy examinations. Representative prostate samplesfixed in 10% neutral buffered formalin were trimmed in the coronal planeperpendicular to the urethra, and 1.5 to 2.5 mm sequential slices werephotographed.

Bilateral coagulation to liquefaction necrosis was observed in bothacute animals (Animals 7C161 and 7C163). There was minimal associatedinflammation and mild hemorrhage. Bilateral multifocal to coalescinginflammation was observed in the subcapsular parenchyma in all sixchronic animals (Animals 7C201, 7C206, 7C197, 7C199, 7C202 and 7C204).There were cellular infiltrates (primarily lymphocytes and macrophages)expanding the interacinar mesenchyme. Moderate to marked such reactionwas observed in Animal 7C202 while the response was minimal to mild inthe multiple sections from the remaining animals from the three chronicobservation periods.

Acinar atrophy characterized by reduction of lobular and sublobularclusters of glands with reduction of lumen and lining with attenuatedcells was a consistent finding in all chronic animals. The intensityranged from minimal to moderate. Moderate acinar atrophy was observed inmultiple sections of all chronic animals except Animal 7C204 from the 60day group, in which the reaction was minimal in four of the fivesections studied.

Bilateral loss of parenchyma leading to formation of cavities waspresent in multiple sections from all six chronic prostate samples.These cavities were variable in size and often coalesced with theadjacent urethra. In most sections, a unilateral cavity merged with theurethra. In a few sections the urethra merged with bilateral cavities oneither side of the prostate. The cavities often were lined byurothelium, possibly a regenerative and reparative response from thecommunicating urethral epithelium. Presence of cavities that representedloss of tissue mass from DC ablation in all the specimens from threetreatment groups suggest the lasting effect of reducing prostate mass byDC ablation over a period of 60 days. Also, there was no significantinflammatory reaction in the tissue surrounding the cavities, suggestingsuch union of necrotic tissue cavity and urethra either did not inciteinflammatory response or the inflammation had receded and resolvedcompletely at the time points of observation. Additionally, the urethrahad one or many of the changes that included epithelial discontinuity inthe form of erosion and ulceration, focal subepithelial inflammation andminimal hemorrhage, intracytoplasmic vacuolation of urothelium over asegment of urethra, focal aggregate of luminal necrotic cellular debris,patchy granulation tissue in the adjacent stroma and a marginal increasein periurethral mesenchyme.

Cystic dilation of glandular acini of variable degrees, ranging fromisolated focal area to a substantial proportion of the remainingprostate gland, was observed in all the animals. These changes werepresent in multiple sections in the same animal. The changes wereminimal in Animal 7C202. The dilated acini were lined by cuboidal toattenuated cells and occasionally contained sloughed cells, cellulardebris and secretory product. Within the atrophic acini, multifocalexpanding islands of regenerating glands were observed in a few animals.The foci of regeneration impinged the adjoining atrophic gland and werecomprised of arborizing acini lined by tall columnar cells with abundanteosinophilic cytoplasm, vesicular nuclei with rare mitotic figures.

The study showed a reduction in the prostatic tissue mass using DCablation as evidenced by loss of tissue surrounding the electrodeinsertion sites and atrophic changes incited elsewhere within the gland.The effects were persistent and observed in multiple sections ofprostates at 20, 40 and 60 days following the treatment procedure. Themerging of device-induced cavities and the urethra is likely a portal ofdrainage for the necrotic tissue mass contributing to the minimizationof the inflammatory reaction in the remaining tissue.

Example 2

A study was performed to determine comparative size of the treatmentregion of a volume of tissue treated with a cathode and a volume oftissue treated with an anode. Beef round samples and in-vitro canineprostates were treated.

The following protocol were used to examine the amount of treated volumein beef round samples and in prostate at both the anode and the cathode:

1a. Treat beef samples with the following currents: 20, 40, and 60 mA.

1b. Treat in-vitro prostates with 40 mA current.

2a. Treat beef samples with the following doses: 36, 72, 108, and 144 C.

2b. Treat in-vitro prostates with 4 and 13 C of dose.

3. Soak samples in formalin solution for a minimum of approximately 48hours.

4. Slice samples with meat cutter into approximately 3 mm slices.

5. Measure thickness of each sample at anode and cathode treatment.

6. Photograph each slice.

7. Measure area of treatment in each sample using Microsoft Visio™software.

8. Calculate volume treated (post-fixation) for anode and cathode.

9. Compare data.

Beef round samples were tested with 12 mm simple Pt Ir pin electrodes.Prostate samples were tested with various pin and coil sizes. Resultsare shown in Tables 7 and 8, below.

TABLE 7 Beef Round Results N N Cathode Cathode (Sam- Anode Anode (Sam-Dose Current Volume Std Dev ples Volume Std Dev ples (C) (mA) (cc) (cc)Tested) (cc) (cc) Tested) 4 20 to 60 0.22 0.04 3 0.15 0.00 3 36 20 to 601.18 0.26 9 1.24 0.18 9 72 20 to 60 2.45 0.47 9 2.33 0.23 9 108 20 to 603.09 0.64 22 3.23 0.93 22 144 20 to 60 3.95 0.29 9 4.23 0.66 9

TABLE 8 Prostate Results N N Cathode Cathode (Sam- Anode Anode (Sam-Dose Current Volume Std Dev ples Volume Std Dev ples (C) (mA) (cc) (cc)Tested) (cc) (cc) Tested) 4 40 0.29 0.24 3 0.24 0.06 3 13 40 0.76 0.17 30.86 0.19 3

FIG. 35 illustrates treatment volume against dose delivered for bothanode treatment and cathode treatment for beef rounds. As shown in FIG.35 there is no significant difference in treatment volumes between theanode and the cathode.

Example 3

A study was performed to determine the effects of delivering a dose atdifferent currents on the amount of treated volume. Beef round sampleswere treated. Protocol used for Example 3 followed the protocol ofExample 2 for beef round samples.

The results of the study indicated that in the range of current between20 and 60 mA, there is substantially no appreciable difference in theresults of treatment.

Results are shown in Tables 9 and 10, below.

TABLE 9 Cathode Results Cathode Cathode Std N (Samples Dose (C) Current(mA) Volume (cc) Dev (cc) Tested) 4 40 0.22 0.04 3 36 20 1.04 0.22 2 3640 1.08 0.15 4 36 60 1.40 0.33 3 72 20 2.33 0.13 2 72 40 2.36 0.42 4 7260 2.65 0.73 3 108 20 2.50 0.37 3 108 40 3.27 0.62 15 108 60 2.85 0.62 4144 20 3.98 0.24 2 144 40 3.86 0.33 4 144 60 4.05 0.33 3

TABLE 10 Anode results Cathode Cathode Std N (Samples Dose (C) Current(mA) Volume (cc) Dev (cc) Tested) 0 0 0 0 4 40 0.15 0.00 3 36 20 1.230.01 2 36 40 1.32 0.21 4 36 60 1.15 0.18 3 72 20 2.08 0.00 2 72 40 2.530.17 4 72 60 2.23 0.11 3 108 20 3.03 0.95 3 108 40 3.31 0.92 15 108 603.04 1.15 4 144 20 4.10 0.13 2 144 40 4.49 0.42 4 144 60 3.97 1.09 3

FIG. 36 illustrates the data in Tables 9 and 10. FIG. 36 illustratescathode results for treatment volume against dose delivered for a 20 mAcathode, a 40 mA cathode, and a 60 mA cathode.

As shown in FIG. 36, the dose to volume relationship is not influencedby the magnitude of current delivered to the electrodes up to 144 C andwith a current between 20 and 60 mA. The relationship between dose andvolume treated is linear. The variation between dose and volumeincreases with dose, presumably due to the sensitivity of the radius oftreatment zone on the volume.

Example 4

A study was performed to determine the margin of safety that the capsuleprovides from causing damage external to the prostate. Canine subjectswere treated.

Two canines were treated with doses that were expected to interact withthe capsule. The following parameters were looked at to determinewhether the dose delivered caused harm to the patient by causingnecrosis to tissues outside of the capsule:

1. Comparison of the ratio between actual treatment and the expectedefficacious treatment.

2. Visual observation of blackened tissue outside of the capsule due totreatment.

3. Visual observation of blackened tissue visible on the capsule.

4. Histological evidence of capsule remaining.

The two canine prostates had transverse widths of approximately 33 mmand 20 mm respectively and were treated with 16 mm coil electrodes.Using these transverse widths and assumptions listed below, a TargetedPrescribed Dose was determined for each prostate.

Assumptions:

a. Treatment diffuses equally from electrode.

b. Tissue dose response is in the range of 18 to 30 C/cc for canineprostatic tissue.

c. Targeted Prescribed Dose incorporates a 10% radius safety margin tothe capsule while preserving a 6 mm diameter in the center of theprostate for the urethra.

d. Targeted Prescribed Dose is the midpoint between the dose resultingin a treatment radius following the above assumptions.

Targeted and Actual Doses delivered to the two subjects are shown inTable 11, below.

Resulting Target and Actual Doses Delivered to the Two Subjects in thisStudy

Targeted Prescribed Actual Delivered Subject Dose Dose Over Dose Subject1 64 C# 70 C 1.1:1  42 C# 1.6:1  Subject 2 16 C# 24 C 1.5:1* 16 C#1.5:1* *Indicates a dose was delivered that was 50% over recommendedaggressive dosing. #Indicates dosing if placement of electrode isabsolute with a 10% safety margin from interaction with capsule tissues##Indicates dosing if placement error of electrode is known and nosafety margin accounted for in dosing

Tissues adjacent to the prostate were affected at the right caudal end.This lobe was treated by the anode. Based on the position and length ofthe anode electrode, and taper of this prostate anatomy, it wasdetermined that the electrode was no further than approximately 2 mmfrom the capsule. If it is assumed that the electrode is 2.5 mm from thecapsule, the predicted target dose may be about 9 C. This calculates toa 2.6 to 1 Over Dose ratio in the right caudal portion of this prostatewith 16 mm electrodes.

After treatment in both subjects, a blackened treatment zone was visibleon the left lateral side of the prostate in Subject 1. Tissue adjacentto this zone appeared healthy. This illustrates that the treatment zonedid diffuse far enough that it interacted with the capsule. The factthat no necrotic tissues were observed in adjacent tissue indicates thatthe hydrogen and hydroxyl ions were contained within the capsule.

The capsule of Subject 2 saw extensive treated tissue up to the capsuleboundary at the cathode, presumably due to both the overtreatment of thecapsule and the electrodes being placed closer to the outer capsule thanthe urethra. This biased the treatment towards the capsule more thanwould be expected with a 10% overdose. The overdose ratio wasrecalculated using the actual distance from the capsule and it was foundthat the cathode in Subject 2 was overdosed by 60%.

Examining the histology in areas where the treatment visually wasadjacent to the capsule was not definitively conclusive due to the factthat the slide preparation process can be destructive to these boundarytissues. Histological evidence and the pathologist's conclusionsindicated that the cellular structures making up the capsule showednecrosis but the capsule's structural integrity was maintained. Thisassessment agrees with the visual observations seen during the procedureand necropsy with the exception of the right caudal portion of theprostate of Subject 2.

In this acute animal study, prostates were nominally overdosed by 50 to60%. No treatment was observed outside of the prostate capsule except inthe localized area where the electrode was very close to the capsule.The estimated overdosing in this localized area was 160%. This indicatesthat, in a small sample size, the canine prostate capsule allowsoverdosing somewhere between 50% and 160% without allowing the treatmentto affect adjacent tissues outside of the capsule. Anecdotal evidenceindicates that the human capsule is more substantial than the caninecapsule.

Example 5

A study was performed to assess various impedance parameters includingdose to failure, effect of length, effect of electrode type, effect ofelectrode diameter, effect of pin diameter, effect of insulation, effectof current and parallel paths,

The Dose to Failure evaluation showed that dose to failure is inverselyproportional to length and diameter of the electrode and is proportionalto the amount of venting. The following equation was determined:

DTF=(Gas Formation-Venting)*current

DTF=(1/(d*L)−(n ² *Δp/l))*I

where:

DTF=Dose Time to Failure

d=diameter of electrodeL=length of electroden=number of electrodesΔp=pressure drop across ventl=length of insulationI=current at electrode

Through empirical testing it was shown that as pin length and diameterincreases the impedance stability of the system increases. Furthermoreas the electrode surface area of the active section increases theimpedance stability increases. With a constant electrode surface area ofthe active sections impedance stability increases with a lower magnitudeof direct current or running multiple electrodes in parallel. With aconstant current and electrode surface area of the active section theimpedance stability increases by decreasing the insulation length fromthe active area back to catheter by allowing the gases to vent out ofthe active area.

Example 6

A study was performed to assess the corrosive properties of nitinol andplatinum-iridium-coated nitinol wires. The study further observed theeffects of parylene-coated electrodes on electrode corrosion and tissuetreatment zones.

Nitinol is commonly used in medicine and is known to corrode at theanode with applied direct current. Platinum is resistant to corrosion.Accordingly, for testing the invention disclosed herein, platiniumridium coated nitinol wires have been employed.

Parylene-C coating has high electroresistivity, is corrosion resistant,has high electrical impedance, and is impermeable to moisture. In thisstudy, parylene-C coating was applied to both nitinol and platiniumiridium electrodes.

Two tests were performed. One test used nitinol wires for both cathodeand anode. The other test used platinium iridium-coated nitinol wiresfor both cathode and anode. The electrodes were inserted into twoseparate gels and run for 120 coulombs at 25 mA. To confirm no corrosionof the platinium ridium-coated nitinol electrodes, a further test wasperformed that was run for 500 coulombs at 25 mA. Pictures of eachelectrode were taken before and after the tests in order to see changesin the appearance of the electrodes. Observations and results weredocumented.

FIGS. 37a and 37b illustrate the nitinol anode before starting the testand after the test was stopped, respectively. The tests were to carry onfor 120 coulombs at 25 mA. After approximately 20 minutes, the currentfor the nitinol electrodes dropped to 0 (zero). This was presumably dueto corrosion of the anode, as illustrated in FIG. 37 b.

The nitinol cathode had no apparent corrosion, nor did the platiniumiridium-coated electrodes. The confirmation test of 500 coulombs at 25mA also resulted in no observable corrosion of either the anode or thecathode.

The parylene-C coating also was found to be a dependable insulator. Theportion of the electrodes that were coated with parylene-C were notactive. No ion exchange occurred in these regions. This was observed atthe start of the tests when the treatment sizes were not so big thatthey overlapped the coated regions. This coating also appeared to have apositive effect on impedance. It appeared that the microscopicinsulation facilitated gas escape, resulting in a lower impedance.

The results showed that the nitinol anode had significant corrosion butthe cathode did not. The platinum iridium-coated nitinol wires had nocorrosion, even after further testing with 500 coulombs.

Example 7

A study was performed to determine the relationship between ease ofelectrode insertion and electrode diameter. Electrodes were insertedthrough the prostate capsule and into the urethra. Pig prostates wereused.

Two pig prostates and urethras were inserted with various diameter pinelectrodes. The resulting ease of piercing through the capsule and intothe urethra was subjectively judged by the individuals inserting thepins into the urethras. Pins were approximately 8 mm in length. Othermethods of introducing the pin into the tissue were tried and judgedrelative to the initial insertion method. These methods include using a0.5 mm diameter needle to pierce through the capsule and into the swineurethra and using a pair of tweezers to pierce and pull the tissuesapart. The ease of insertion was then subjectively ranked by twoindividuals, each of whom did the trials independently, with a rank of10 being the easiest to insert and a rank of 1 indicating nearlyimpossible to insert.

Results are shown in Table 12, below.

TABLE 12 Insertion 0.5 mm 0.8 mm 0.3 mm Ptlr Coated Method Ptlr Pin PtlrPin NiTi Normal 6, 8 4, 6 1, 1 Needle Pierced 8, 7 6, 6 8, 1 Tweezers 8,9 8, 9 2, 7 Test Subject: Subject 1 (First Number); Subject 2 (SecondNumber)

Both subjects ranked the diameter of electrodes in the following order:Best 0.5 mm Ptlr Pin, 0.8 mm Ptlr Pin, Worst—0.3 mm Ptlr Coated pin.

The 0.5 mm diameter pin provided substantial stiffness such that theelectrode did not buckle. The 0.8 mm pin did not insert as easily as the0.5 mm pin, presumably because the created hole is larger. It ishypothesized that if the tip of the 0.8 mm pin was sharpened or tapered,it could perform as well as the 0.5 mm pin. The 0.3 mm pin provided verylittle stiffness or mechanical advantage and buckled. This pin wasunable to be inserted. Using a needle or tweezers to create a pilot holewas only incrementally better as it was difficult to find the hole.

Example 8

Initial human feasibility studies using DC ablation in the prostate withthe Neuflo™ System (a transurethral DC Ablation system) have beenconducted in Santiago, Chile. A summary of the studies conducted isgiven in Table 13.

TABLE 13 Table: Human Feasibility Studies Summary Study ObjectivesSubjects Method Findings Stage 1: Ex Vivo 1. Validate tissue 3.Prostates Treat with DC 1. Histological post Radical response in humanablation using pin evidence of Prostatectomy prostate tissue. electrodesinserted liquifactive and (RP) study of through the coagulativeelectrodes capsule necrosis immediately post 2. Obtained a RP. initialcharge setting Stage 2: In Vivo 1. Evaluate 5 Subjects with Treat withDC 1. Histological study of electrodes Treatment charge Prostate Cancerablation using pin evidence of during RP setting electrodes insertedliquifactive and 2. Evaluate through the coagulative Impedance capsuleduring RP necrosis 2. Necrosis stayed within the capsule 3. Verifiedacceptable impedance Stage 3: 1. Verify 4 Prostates Treat with TU 1.Histological Transurethral Ex electrode Catheter evidence of Vivo studyof DC placement and immediately post liquifactive and Ablation post RPurethral puncture RP coagulative with Neuflo necrosis catheter 2.Urethral 2. Determine puncture method optimal prostate was successfulsize 3. Prostate size 30-65 cm³ and sizing inc/exc criteria FeasibilityStudy 1. Optimize Up to 25 BPH Treat BPH with 1. Obtained of the TU DCtreatment subjects TU Catheter. treatment Ablation System in parametersFollow subjects for parameters for US BPH subjects 2. Obtain 1 yearstudy preliminary safety 2. Obtained and efficacy data preliminarysafety 3. Assess and efficacy data Discomfort to utilized for hypothesistests for the US study 3. Procedure was well tolerated

Stage 1 of the DC Ablation human studies involved treating three (3)human prostates with pin electrodes immediately post-radicalprostatectomy (RP) for prostate cancer. Results showed the ability of DCablation to induce consistent necrotic lesions within both malignant andbenign prostate tissue.

Stage 2 of the human studies (in vivo) was conducted by treatingpatients prior to radical prostatectomy with pin electrodes to examinetissue response in living human prostate tissue. Immediately followingDC ablation treatment, the prostates were removed as RP commencedfollowing treatment completion.

Results from the first two stages of human prostate tissue study areshown in FIG. 38 with the upper trend line representing the cathodenominal expected radii and the lower trend line representing the anodenominal expected radii.

Human prostates were treated ex vivo (Stage 3) and in vivo duringradical prostatectomy (Stage 4) with a Transurethral DC AblationCatheter to more accurately represent future treatments; and to optimizeelectrode placement and monitor the safety of the placement of needlesnear the bladder and urethra.

FIG. 39 is an in vivo image illustrating the necrosis volume achieved bythe transurethrally ablating tissue with DC ablation.

Sixteen BPH patients were treated with a transurethral DC ablationsystem to investigate the safety and efficacy of using a TU DC ablationsystem as a treatment for BPH. Prostate sizes ranged from 30 to 90 cm³.The procedure was administered in an office setting using a topicallidocaine gel in the urethra. No oral sedative or local nerve block wasrequired. Patients reported mild to no pain during the treatment.

Preliminary symptomatic relief data, as shown in Table 14, suggests thatpatients experienced symptomatic relief one week after treatment.

TABLE 14 BPH Feasibility Study Initial Efficacy Data (Treatment Rate =25 mA) 1 week (n = 13) 1 month (n = 10) 3 month (n = 3) Mean ± SD Mean ±SD Mean ± SD Baseline (n = 13) (Paired % (Paired % (Paired % ParameterMean ± SD improvement) improvement) improvement) AUA Symptom 24.1 ± 4.8 14.3 ± 5.6 14.3 ± 5.6 7.7 ± 5.0 Score (38%) (37%) (65%) QOL 5.0 ± 0.8 2.8 ± 1.7  2.3 ± 1.7 0.7 ± 0.6 (44%) (54%) (86%) Qmax 9.6 ± 3.5 12.1 ±2.5 13.7 ± 4.3 9.7 ± 5.0 (26%) (43%) (1%)

In addition, 3 subjects were treated within the OUS study in which thetreatment rate was 40 mA. Based on the subject's transient (1 week)increase in symptoms, quality of life and their diminished ability tourinate, a decision was made to utilize a treatment rate of 25 mA.Initial safety data revealed no severe adverse events in the first 16patients treated at 25 mA and 40 mA. Urological adverse events arelisted in the Table 15.

TABLE 15 Table: Urological Adverse Event Frequency (Treatment Rate = 25mA and 40 mA) Timepoints* 1 week (n = 12) 1 month (n = 12) 3 month (n =6) Adverse Event (mild/mod/severe) (mild/mod/severe) (mild/mod/severe)Hematuria 17%/0%/0% 0%/0%/0% 0%/0%/0% Dysuria 55%/23%/8% 40%/20%/8%17%/0%/0% Pelvic Pain 31%/0%/0% 20%/0%/0% 0%/0%/0% Bladder 23%/23%/0%0%/0%/0% 0%/0%/0% Spasms Urgency 8%/15%/0% 8%/0%/8% 17%/0%/0%Incontinence Incontinence 0%/0%/0% 0%/0%/0% 0%/0%/0% Urinary 0%/0%/0%0%/0%/0% 0%/0%/0% Infection Acute 0% 0% 0% Retention *includes monitoreddata only

1. A non-implantable minimally invasive system for treatment of issue ina body via direct current ablation comprising: a catheter for insertioninto the body wherein a portion of the catheter remains outside of thebody when the catheter is in a treatment position proximate the tissueto be treated; between 2 and 12 electrodes positioned for deploymentthrough and outwardly from the catheter, wherein an active area of atleast one electrode delivers a charge to impart a high pH or a low pHsuch that a necrotic zone is created to form a field of treatment; apower source for receiving treatment parameters and applying directcurrent and power to the plurality of electrodes based on the treatmentparameters, wherein the direct current is applied at a magnitude ofbetween approximately 10 and 50 mA per electrode and the power isapplied at between approximately 20 and 3200 mW of power per electrodeto deliver between 15 and 90 coulombs of charge per electrode, afixation element operably associated with the catheter for maintainingthe catheter in a treatment position during treatment; wherein theablation of tissue using the system is substantially non-thermal. 2-55.(canceled)